Managing Pain with Cannabis
By Diana Hahn and Stacey Marie Kerr MD
Chronic and/or debilitating pain is the most prevalent use for medical cannabis in the state of Hawaiʻi. Advances in modern medicine have allowed us to slow disease progression, to transform life-threatening conditions to long-term chronic ones, and to survive traumas that would have been fatal a generation ago.
Chronic pain goes far beyond the physical toll on an individual’s body. Limited mobility, limited productivity, and depression all affect individuals, families, and society both financially and emotionally. Abuse and addiction to pain medications compound the problem, sometimes leading to fatal consequences. Therefore, it is imperative that physicians and patients continue to find safe and effective ways to treat and manage chronic pain.
The Endocannabinoid System, Phytocannabinoids, and Pain
The endocannabinoid system is intricately involved in the regulation of pain and in inflammation. There is even evidence that is leading scientists to propose that certain chronic pain conditions may represent abnormalities in the endocannabinoid system. 
Both of the known cannabinoid receptors (CB1 and CB2) play a role in the perception of pain, making the cannabinoids that bind to these receptors effective at reducing our perception of pain. Although there is clinical data that shows the efficacy of cannabis as an analgesic, the mechanisms through which they act appear to be complex and varied, encompassing not only cannabinoid receptors, but other pathways as well. Scientists are still working to piece together the various ways that cannabinoids affect pain perception.
THC, CBD and beta caryophyllene (a terpene present in cannabis) have all been shown to reduce pain. In general, THC has a higher affinity for CB1 receptors that are concentrated in the brain and central nervous system. THC’s analgesic effects may also operate through interactions with chemicals that activate opioid receptors. CB1 receptors outside the brain also appear to have an effect on pain in the gastrointestinal tract. 
CBD has a lower affinity for both CB1 and CB2 receptors, however it appears to exert its effects by inhibiting anandamide (an endogenous cannabinoid, or endocannabinoid) deactivation or otherwise enhancing anandamide’s activities. CBD that does bind to CB2 receptors may also act as an anti-inflammatory and therefore has some analgesic properties.  The terpene β-caryophyllene binds to the CB2 receptor, and has been shown to have anti-inflammatory and analgesic properties similar to CBD.
Delivery Methods for Pain
Delivery methods have significant differences in time of onset as well as how long the beneficial effects of cannabis will last. When choosing a delivery method, patients should take into account how quickly they are seeking relief, how long they want the medication to be effective, how often they want to medicate, and the potential effects/side effects of each different delivery method. Patients have reported that some delivery methods work better for their pain than others, so it is important to experiment and find what works best for you. The following chart gives general guidelines to help you make your choices.
|Delivery Method||Onset Time||Peak||Duration||Drawbacks|
|Inhalation||A few seconds to minutes||30 minutes||2-3 hours||Smoking or vaporizing can cause lung and throat irritation|
|Ingestion||30 minutes to 2 hours||Variable||5-8 hours||Onset, duration, and effects are difficult to predict/control|
|Topical||A few minutes (locally)||Unknown||1-2 hours||Analgesic effect is limited to localized area|
|Sublingual||10-45 minutes||Unknown||2-8 hours||Variable duration and onset time|
Types of Pain
Patients registering for medical cannabis are using it to treat many different types of pain. Hawaiʻi law does not specify causes or types of pain, just that a patient’s pain must be severe and chronic or debilitating.
Cannabis has been shown to be more effective in treating certain types of pain and less effective with others. Below is a list of common types of pain for which there is evidence of cannabis’ efficacy or inefficacy. Please note that some categories overlap (e.g. HIV/AIDS pain is often neuropathic).
Acute pain is defined as a sharp and/or sudden pain that resolves relatively quickly. Examples of acute pain would be a cut or a burn. Cannabis has not been shown to be effective in reducing acute pain, and in some cases may have a hyperalgesic effect, actually increasing the sensation of acute pain.
Cannabis has been shown to be effective at treating pain related to cancer. Cannabinoids can increase a patient’s chronic pain threshold, effectively giving the patient a lower perception of pain. In animal studies, cannabis was as effective as codeine at controlling cancer-related pain. Cannabis is useful in managing other symptoms of cancer and many of the side effects of cancer treatment such as nausea and wasting syndrome.
Fibromyalgia is one of the most common conditions for which patients in chronic pain clinics use medical cannabis (along with degenerative arthritis, MS and spinal cord injury). Although there is limited scientific evidence to support the effectiveness of cannabis in treating fibromyalgia, the anecdotal evidence points to relatively high efficacy. In a survey of fibromyalgia patients, 62% reported cannabis as “very effective” in treating symptoms compared to 8-10% reporting the leading pharmaceutical drugs to be “very effective.”
Cannabis offers pain relief for a significant number of HIV/AIDS patients. In one study, 90% of HIV/AIDS patients inhaling cannabis reported an improvement in nerve pain.  CBD in particular is reported to be helpful for HIV neuropathy pain. Cannabis has produced better results for this patient population than over-the-counter and prescription pain medications. HIV/AIDS patients often deal with adverse side effects to many medications, and cannabis appears to be fairly well-tolerated for this patient group. In the study mentioned above, the most frequently occurring side effect of cannabis was memory deterioration, however it occurred at a tolerable level and did not stop patients from using cannabis.
Multiple Sclerosis Pain
Cannabinoids can help relieve MS-related pain, as well as playing a role in managing spasticity and tremors. CBD may also protect against neuro-inflammation, helping to manage the symptoms of MS.
The majority of existing data in regards to cannabis and pain comes from patients with chronic neuropathic pain, arising from a variety of conditions. Cannabis used for neuropathic pain has consistently proven to have an analgesic effect; in a review of 18 randomized-controlled clinical review trials, 15 concluded that cannabis had a significant analgesic effect compared to placebo. 
In general, CB1 receptors are upregulated (increased) and CB2 agonists (activators) induce analgesia around nerve injuries. Introducing more agonists (cannabinoids that plug into and activate these receptors) reduces pain. There is evidence that cannabinoids administered in combination with each other and terpenes (i.e. whole plant medicines) provide more relief for neuropathic pain than single compound medicines.
Cannabis has not been shown to be effective in treating post-operative pain. 
Rheumatoid Arthritis pain
Clinical trials have shown that cannabis limits rheumatoid arthritis disease activity as well as working as an analgesic. Along the same lines, it “appears [that] the endocannabinoid system is intimately involved in tissue healing in the face of inflammatory conditions, correlating clinically with prevention and treatment of inflammation-mediated pain.” 
Sickle Cell Disease pain
A survey showed that 52% of patients with sickle cell disease using cannabis are using it to reduce or prevent pain (other reasons were to aid/improve sleep, mood, and relaxation). SCD patients are often treated with opioids, and there is potential to introduce cannabis as an alternative/synergistic analgesic as well as to counteract the nausea from opioids. Cannabis’ anti-inflammatory properties seem to be helpful for SCD as well. Cannabis may even favorably modify the central and peripheral mechanism of the disease. 
Harm Reduction: Cannabis and Opioids
Treating severe pain effectively can be challenging as well as frustrating. For many patients, opioids are the only pharmaceutical option available to manage their level of pain. Opioids, however, prove ineffective and/or intolerable for a significant percentage of patients. They also pose a serious risk of dependency, abuse, and/or overdose. From the CDC:
In 2014, almost 2 million Americans abused or were dependent on prescription opioids.
As many as 1 in 4 people who receive prescription opioids long term for non-cancer pain in primary care settings struggles with addiction.
Every day, over 1,000 people are treated in emergency departments for misusing prescription opioids.
In light of this, cannabis is a promising, safe alternative or complimentary therapy that can lower or even replace opioid doses as well as provide an alternative for those who cannot tolerate opioids at all.
Cannabis and opioids have been shown to work synergistically for many patients, though this may not be true for all. Patients who benefit from cannabis in addition to opioids may see an increase in the analgesic effect of opioids, allowing them to decrease the dosage and/or frequency of the opioid. They may also note a decrease in opioid side effects making them more tolerable.
THC has specifically been shown to enhance the efficacy of fentanyl and buprenorphine patches.  It is important to be aware of drug/drug interactions with cannabis and many other analgesics and opioids, since they may utilize the same metabolic pathways and therefore require dosage adjustments.
We know cannabis can help with pain. “Cannabinoids have proven to be effective analgesics in a number of studies, and have been shown to inhibit pain in virtually every experimental pain paradigm in supraspinal, spinal, and peripheral regions.”  We also know cannabis has an excellent safety profile. “In a survey of studies involving cannabis, 96.6% of adverse effects were non-serious and generally described as transient and well-tolerated. Most patients who participated in cannabis trials were able to complete the trial, compared to a withdrawal rate of 33% on average for opioid trials.”  In light of these facts, cannabis may even be a good treatment option to consider before opioids for certain patients.
Cannabis is medicine, and all medicine must be respected and used with careful intention. While there have been no reports of cannabis toxicity deaths, and while the vast majority of adverse reactions have been mild, it is important to note that some of the most serious adverse side effects can be cognitive, psychomimetic (causing symptoms of psychosis), and/or substance abuse related.
These extreme side effects are most likely to occur in patients who are adolescents and/or have a history of mental health disorder or addiction. The most effective introduction of cannabis for pain is best achieved with the assistance of a health care provider who has knowledge of clinical cannabinoid medicine.
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