For centuries, the cannabis plant has been used in traditional medicine as a pain reliever. However, research studies have shown that cannabis only acts as a pain reliever in a very narrow range of pain types. One of the reasons for the paradoxical nature of cannabis in the treatment of pain has been the lack of disambiguation between the action of individual cannabinoids. The reasons how and why cannabis works for pain are quite complicated, and there are major differences between the actions of the psychoactive compound Tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). In this article, we will explore the effectiveness, applications, and limits in using THC to treat pain.
It is important to note that, although cannabis and THC have been used medically for thousands of years, research is limited. Because of the scheduling of cannabis (or marijuana is US legal nomenclature) by the US and UN, research into the substance has been restricted for about over five decades. Hopefully those restriction are starting to be lifted as it becomes more clear that the plant poses very few threats to public health.
What Types of Pain can be treated with THC?
One of the main reasons for cannabis legalization across the US and around the globe is for the treatment of pain. In fact, even a book put out by the National Academies Committee on the Health Effects of Marijuana stated that there is “‘conclusive or substantial evidence’’ that cannabis is effective for the treatment of chronic pain. This use goes back more than 4,000 years to the ancient Chinese who wrote about using the seeds to relieve pain. Since then, it has been used by a variety of cultures, in many different ways, but pain has always been one of the primary driving forces.
Today, more than 100 million US adults report being affected by chronic pain, but there are limitless causes of this pain. For our purposes, we will focus on the parts of the body through which pain is expressed. These are the nociceptive, neuropathic, and central systems. The nociceptive system expresses pain when there is damage to bodily tissue, such as injuries or physical trauma. This is the most common type of pain, and is usually a sharp or throbbing pain, for which the cause can be readily known. For this type of pain, tissue damage causes a signal to travel through the nerves to the brain where it is interpreted. Next, proinflammatory compounds from the immune system are released to the area for healing and damage control. This system has evolved as a warning and self-protection system for our bodies.
Neuropathic pain is more complicated, and involves disturbances within the peripheral nervous system. Generally, this is caused by trauma or disease to the somatic nervous system, resulting in improper signaling between the brain and parts of the body. Neuropathic pain generally does not provide any valuable warning signals, tends to be chronic and persistent, and is one of the hardest types of pain to treat.
Central pain is caused by injury or illness that affects the central nervous system, the brain and spinal cord. With this pain, the pain signal may be perceived even if there is no peripheral cause, such as in the case of Fibromyalgia. Often the analogy for this type of pain is to an electric guitar amp. The electric guitar itself is not a loud instrument (like the pain) but the amp you plug it into (the central nervous system) can mean a whole stadium can hear it.
To further complicate everything, pain is sort of a subjective occurrence in many respects. It can only be perceived by the individual, each person has different responses to pain, and cannabis will affect each pain and each person differently.
How does THC treat pain?
When the cells of our bodily tissues are damaged, they actually release endogenous cannabinoids, or ECBs. These ECBs modulate the signaling of the nerves through the CB1 and CB2 type receptors of the endocannabinoid system. This in turn has an analgesic effect to suppress sensation, acting as a sort of gate-keeper for signaling to the brain and controlling the immune responses such as inflammation. Likewise, the cannabinoids in the Cannabis sativa plant can also modulate this pain response. So, even without all the anecdotal reports on cannabis use for pain management, it is probably a good place to look in the search for effective novel pain medications.
A 2017 review looked at more than 28 published studies covering more than 2,454 patients with chronic pain reporting to clinics. It found that cannabis use was associated with a reduction in pain (37% vs 31% and a reduction in numerical pain scale self-reporting. But it was also noted that it was not effective with all pain types.
In a double blind clinical trial from 2007, 15 volunteers were asked to smoke various strengths of cannabis before being injected with capsaicin, the compound that gives chilies their spice. This was done to simulate nociceptive type pain. Five minutes after smoking the cannabis there was no effect on pain at any level of THC strength. At 45 minutes there where mixed results, with the medium strength cohort reported significant decreases in pain levels, and the high dose cohort reporting significantly higher levels of pain. There was no change from baseline at the low dose level. This study, illustrates that the effects of THC on pain is paradoxical. That it was shown, at least in this study, to be effective at medium doses, but counter-indicated at higher doses.
In a similar study, 18 participants were given 20 mg of oral THC or placebo and were given an artificial sun burn using a UV-B bulb to simulate nociceptive pain. In this study, there was no difference between the groups given cannabis and the ones given a placebo. Furthermore, there was some indications that the cannabis group experienced hyperalgesia, or increased sensitivity to pain. This increased sensitivity to pain from THC was also seen in a study comparing various analgesics side by side.
So, for nociceptive pain such as injury and trauma, it would appear that the effects of THC are limited, and may even be counter-indicated for some individuals due to hyperalgesia or increased risk of adverse events due to its psychoactive properties. If this is true, than why are so many still using THC to treat pain?
THC and Chronic Pain
That 2017 review went on to state that, in the literature, chronic pain was the most often cited in the use of cannabis. Chronic pain is generally associated with the neuropathic and central systems. The pain that is hardest to diagnose and treat. Here, more promising studies have been performed.
In 2015 study, 16 patients with painful diabetic peripheral neuropathy were given aerosolized THC to treat pain in various concentrations, or were given a placebo. The results showed significant reductions in pain, both in terms of spontaneous or background pain, and evoked pain caused during the experiment. This resulted in a large decrease in pain with the high dose THC of nearly 70%, compared to a 52% reduction from baseline with the placebo. The effects on evoked pain were more variable from patient to patient, and although some patients saw much relieve, once averaged across the group the results were insignificant. That study did go on to conclude that cannabis shows some promise in the treatment of neuropathic pain, and warrants further study. In another study from 2016 on chronic pain involving 42 subjects with central neuropathic pain related to spinal cord injury and disease, similar conclusions were made.
In one of the most interesting studies to date, 17 patients were given a THC sublingual tincture and assessed for chronic pain. They were then given similar behavior tests as the above studies, but additionally they were placed in an fMRI to see how their brain function was affected. Their results also showed a significant decrease in pain with the THC group but not the placebo one. But what was really amazing is that they could actually see this process going on in the brain scanner.
These researchers found that THC modulates pain response not necessarily by stopping the transmission of signals from the peripheral nervous system to the brain, but between parts of the brain. What they observed was a reduction in functional connectivity between a part of the brain called the anterior cingulate cortex (ACC) and the sensorimotor cortex. These are the parts of the brain responsible for, among other things, emotion and interpreting the signals from the body. Unlike the other studies that where ambiguous about a dose response curve, this one clearly showed that the degree of reduction was predictive of the response to THC.
To date, there are many studies on the use of THC to treat neuropathic pain, most of which showed significant improvements with only minimal, and transient side effects. Now, because of the last study we may even know where to start looking for a mechanism to better understand the effects of THC on pain.
Does it matter if it is smoked or eaten?
The route on ingestion does play a major role in the effects of THC on the body. Smoking is of course associated with increased risk, but it is also the fastest route of administration. With smoking and vaping, THC is directly absorbed into the blood stream through the lungs. This is results in a peak blood serum concentration within about 6 minutes, and strong effects lasting about 120 minutes. In studies, this results in a steep drop in pain within the first 15 minutes, followed by a slower decrease in pain over the next 2 hours.
Conversely, oral ingestion requires that THC is first transported through the gut to the liver. From there it is metabolized into 11-hydroxy-THC. This results in a delayed and highly variable onset and offset of action. It also means that it is harder to titrate dosage and leads to increased side effects. This means that medical patients should work with their doctors to decide which route of administration is right for them.
What did we learn about THC and pain
So, to review, THC in cannabis is the most widely used illicit substance in the world, with many medical users claiming to use it for pain control. However, results have been mixed when evaluating the quantitative effect of THC to treat pain. It would appear that with injuries, or nociceptive pains like cuts or bruises there is some animal study data to show it is effective. However, in human studies this is not reproduced, and at high doses has actually been shown to increase pain sensitivity. But, for the millions suffering from chronic pain, THC does show significant evidence for decreasing pain response and increasing quality of life. It appears to be safer than many over the counter or prescription analgesics, and does not carry the overdose risk of opioids or the GI lesions and cardiac events associated with NSAIDs. For these reasons, the self-administration of cannabis as a medicine by those suffering from so many diseases such as cancer, multiple sclerosis, dementia, Fibromyalgia, and others are now being justified. As such, it is important that we petition our governments to not only decriminalize the medical use of cannabis and THC, but to expunge the records of those previously convicted of possessing it.
If you enjoyed this article, please also see our article on using CBD to teat pain.