CBD for Pain Relief - A pharmacological or a psychological action?

Formulations using cannabis have been used in clinical settings to study its efficacy in reducing pain when traditional options have failed [1].

Pain is a complex phenomenon with several dimensions influenced by psychological and biological factors. For example, pain intensity reflects a "sensory" dimension of pain, while its unpleasantness represents an "affective," or emotional aspect of pain.

A study published this year led by Syracuse University researchers sheds light on the ability of CBD to reduce pain along with the impact that the so-called placebo or expectancy effect may have on pain outcomes.

Martin De Vita, a researcher in the psychology department in the College of Arts and Sciences, along with Stephen Maisto, research professor and professor emeritus of psychology at Syracuse University, were uniquely prepared to answer the question of "Is CBD analgesic pharmacological or psychological?"

The pair, along with fellow lab member and doctoral candidate Dezarie Moskal, who previously conducted the first systematic review and meta-analysis of experimental research examining the effects of cannabinoid drugs on pain and found positive effects but could not answer if it was pharmacological primarily or placebo effects.

As the first experimental-pain trial to examine CBD's effect, their study yielded noteworthy results. The data showed that CBD and expectancies for receiving CBD do not significantly reduce experimental pain intensity but do make the pain feel less unpleasant.

De Vita and Maisto used sophisticated equipment that safely induced experimental heat pain, allowing them to measure how the recipient's nervous system reacts and responds to it. Experimentally, the drug is administered - in this case, pure CBD - or a placebo and then re-assess the pain responses and see how they change based on which substance was administered. The researchers then took it a step further by manipulating the information given to participants about which substances they received. In some cases, participants were told that they got CBD when they received a placebo or told a placebo when they got CBD.

They found improvements in pain measures caused by the pharmacological effects of CBD and the psychological placebo effects of just expecting that they had gotten CBD [2]. According to De Vita and reported in ScienceDaily, "It is not sunshine and rainbows pleasant, but something slightly less bothersome. We replicated that in this study and found that CBD and expectancies did not significantly reduce the volume of the pain, but they did make it less unpleasant -- it did not bother them as much."

In the study; Medical Cannabis for the Management of Pain and Quality of Life in Chronic Pain Patients: A Prospective Observational Study Ramin Safakish, MD et al. reported that a total of 751 chronic pain patients initiated medical cannabis treatment, and their pain inventory results were documented over a year. In addition, the participants completed the Brief Pain Inventory and the 12-item Short Form Survey (SF-12), as well as surveys on opioid medication use and adverse events, at baseline and once a month for 12 months.

Results of taking medical cannabis (also containing THC) treatment was associated with improvements in pain severity and interference (P < 0.001) observed at one month and maintained over the 12-month observation period. Significant improvements were also observed in the SF-12 physical and mental health domains (P < 0.002) starting at three months. In addition, significant decreases in headaches, fatigue, anxiety, and nausea were observed after initiation of treatment (P ≤ 0.002). In patients who reported opioid medication use at baseline, there were significant reductions in oral morphine equivalent doses (P < 0.0001). The authors concluded that the cumulative evidence supports plant-based medical cannabis as a safe and effective treatment option and potential opioid medication substitute or augmentation therapy for managing symptoms and quality of life in chronic pain patients [3].

CBD may be beneficial for severe chronic or intractable pain of neuropathic origin.JAMA's systematic review of cannabinoids and analgesia, titled Cannabinoids for Medical Use: A Systematic Review and Meta-analysis, assessed 28 clinical trials. The review concluded that there was moderate-quality evidence to support the use of cannabinoids to treat chronic pain and spasticity [4].

Other unpublished clinical studies show pain scores are moderately reduced, whereas the quality-of-life scores are more significantly benefitted. For example, the Maine Medical Center analyzed the results of 1,500 opioid users, taken for chronic pain, and found a reduction in the use of several pain and mood-related drugs:

Opioids: 76.7%
Anxiety meds: 71.8%
Depression meds: 37%
Sleep meds: 65.2%
Migraine meds: 66.7%
Alcohol: 42%

While the pain PDI scale: pain was only moderately reduced, the quality-of-life PSQI scale showed significant (P < 0.003) improvement, suggesting, as reported in the Syracuse University study, there is a significant positive affect component in the way that CBD assists those in pain.

CBD does not pose a risk for addiction or dependence, hence its legalization. Indeed, several studies show a reduction of opioid use in those taking CBD. Furthermore, CBD has been found safe when used in conjunction with opioids in several published studies.

Mechanisms of action of CBD

Cannabinoid receptors primarily mediate the analgesic effect of cannabinoids via inhibition of presynaptic gamma-aminobutyric acid (GABA) and glutamatergic transmission [5].

There are two cannabinoid receptors (CB), CB1 and CB2, found in the human body. CB1 receptors are predominantly expressed in CNS, and CB2 receptors are found mainly outside the CNS. Moreover, activation of these receptors is believed to have anti-nociceptive effects in controlling the human perception of pain. Studies have also shown, these receptors play an essential anti-inflammatory role in chronic pain conditions [6].

CBD has also been demonstrated to have direct agonistic activity on many cell-surface receptors, including the serotonin 1A receptor (5-HT1A), the adenosine A2A receptor and the peroxisome proliferator-activated gamma (PPAR-γ) receptor, all of which are associated with anti-inflammatory pathways, and serotonin 1A receptor with anxiety reduction.

One important note to also consider is the source and form of the CBD.
CBD Liquid Oil products commonly take 2-3 hours before they become effective due to slow oil absorption. In addition, commercially available CBD products differ in their content, dosage, and purity, so results will be different for different CBD products, depending on what other compounds they may or may not contain.

Mechanisms of action of CBD

Cannabinoid receptors primarily mediate the analgesic effect of cannabinoids via inhibition of presynaptic gamma-aminobutyric acid (GABA) and glutamatergic transmission [5].

There are two cannabinoid receptors (CB), CB1 and CB2, found in the human body. CB1 receptors are predominantly expressed in CNS, and CB2 receptors are found mainly outside the CNS. Moreover, activation of these receptors is believed to have anti-nociceptive effects in controlling the human perception of pain. Studies have also shown, these receptors play an essential anti-inflammatory role in chronic pain conditions [6].

CBD has also been demonstrated to have direct agonistic activity on many cell-surface receptors, including the serotonin 1A receptor (5-HT1A), the adenosine A2A receptor and the peroxisome proliferator-activated gamma (PPAR-γ) receptor, all of which are associated with anti-inflammatory pathways, and serotonin 1A receptor with anxiety reduction.

One important note to also consider is the source and form of the CBD.
CBD Liquid Oil products commonly take 2-3 hours before they become effective due to slow oil absorption. In addition, commercially available CBD products differ in their content, dosage, and purity, so results will be different for different CBD products, depending on what other compounds they may or may not contain.

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