Pain
Category
Autoimmune, Inflammatory, Skin
REVIEWED BY
Our Biomedical Sciencetist
Reviewed based on
Literature Discussion & Clinical Trials
Last update
December 2020
What is Pain
A broadly recognized definition of pain is proposed by the International Association for the Study of Pain (IASP): “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.1
Symptoms
Symptoms of pain can differ between people. Given the subjectiveness of pain, the symptoms vary greatly but common non-verbal symptoms may be:2
- Distortion of facial grimace
- Whimpering, groaning, and moaning
- Constant movement e.g. restlessness and distress
- Uneasy and tense appearance e.g. kicking
- Actively avoiding physically touching the area of pain
In addition, the symptoms of pain may be described as a feeling of pinching, soring, stinging, or throbbing in either a local area or a general feeling in the entire body. The range of pain is very broad. It can appear acute, consistent, or chronic and it can vary in magnitude depending on the pain tolerance which differs between people.3
How underlying aspects may interfere with pain perception?
The pain experienced by individuals must always be accepted and respected as it is perceived.
However, it is important to understand the role of underlying factors that may influence pain perception including but not limited to:4
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- The individual’s concept of pain and how it may appear
- Nociception and pain must not be mistaken, as pain is not limited to an unpleasant activity in the sensory nervous system
- Even if the pain may be perceived as a local unpleasantness, it can also affect other aspects of life greatly
- Pain can be expressed in several ways that are not verbal meaning that pain can be felt without the ability to express it
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The connection between Cannabinoids & Pain
Studies find that CBD and THC may have great therapeutic potential and may be used to help treat Pain. CBD and THC are well-known cannabinoids, however, they do not have the same psychoactive effects. THC is psychoactive while CBD does not possess psychoactive effects. According to WHO guidelines, the cannabidiol CBD is generally well tolerated with a good safety profile.
Evidence supports the role of endocannabinoids in pain modulation as the cannabinoid receptor CB1 is present in the nervous system. Therefore, cannabinoids may provide a promising treatment for conditions associated with pain.5
Preclinical- and clinical data propose that the cannabinoids THC, CBD, and to some extent CBG may be therapeutic in the treatment of pain. However, more studies need to be conducted to understand the full potential of cannabinoids in pain management.6
The literature discussion is an overview of the published results from scientific studies investigating if and how cannabinoids can be beneficial in the treatment of Pain. The overview will be updated regularly to ensure the newest and most accurate information.
Endocannabinoids and cannabinoid receptors show therapeutic potential in pain
As discussed by Chen et al., Kohnz, R., Et al., Mulvhill, M.M., Et al., pain, cancer, neurodegenerative diseases, ischemic injuries, inflammation, anxiety, nausea, and drug-withdrawal symptoms can possibly be treated by MAGL inhibitors, which showed potential therapeutic action.7,8,9
Bertolini et al., discussed that the analgesic action of paracetamol can be prevented through blocking CB1 , proposing that CB1 is needed for analgesia.10
Similarly, Fowler et al., mentioned that the breakdown/hydrolysis of anandamide can be blocked by ibuprofen, which may contribute to the analgesic properties of ibuprofen.11
Potential synergistic effect between the opioid- and endocannabinoid systems in pain management
In a study by Reche et al., with mice, the analgesic effect of THC was found to be potentiated by inhibition of opioid-degrading enzymes, proposing that there is a synergistic effect between the opioid- and endocannabinoid systems in pain management.12
Using a rat model, Bagüés et al., showed that muscle pain can be inhibited by THC through activation of CB1.13
Murineddu et al., appraised that several synthetic CB2 agonists have obtained a patent due to their analgesic effects, showing that CB2 plays an important role in pain management.14
De Petrocellis et al., proclaimed that there is an interaction between TRP and cannabinoids (endo and phytocannabinoids) with varying affinities. This means that TRPs can be excellent targets and plant cannabinoids excellent substrates to manage pain.15
Ghafouri et al., discussed that a decrease in pain intensity was connected to high levels of PEA via the PPARa receptor in patients with chronic widespread pain.
In a study by Deliu et al., with rats, algesia can be reduced through blocking GPR55, signaling, proposing that GPR55 is a target to control pain.17
High bioavailability of CBD when administered transdermally and intranasally
In vivo studies by Paudel et al., aimed to evaluate nasal and transdermal permeation using rats and guinea pigs, respectively. Intranasal delivery of CBD showed a bioavailability of 34-46% with CBD being absorbed within 10 minutes. Polyethylene glycol formulation in rats showed a bioavailability of 100% and the use of enhancers did not improve bioavailability. Transdermal gel application in guinea pigs showed that the steady-state plasma concentration of CBD was sufficiently high for this administration route for CBD to be considered beneficial for treating chronic pain. Furthermore, it was demonstrated that with the use of enhancers, the steady-state concentration of CBD was increased by 3.7-fold. This shows that CBD could be successfully administered intranasally or transdermally.18
Clinical trials are research studies that examine new treatments and evaluate their effects on human health outcomes.
Many clinical trials have assessed the effectiveness of cannabinoids to inhibit pain with different results.
CBD and THC show great potential in inhibiting chronic- and acute pain
The most effective effect can be produced by THC and CBD mixture.
Moreover, cannabinoids may be more effective in inhibiting chronic pain than acute pain.
Finally, cannabinoid combination with other pain medications such as opioids, paracetamol, ibuprofen can be used to exhibit a stronger effect to relieve pain.
Cannabis extract and THC show great potential in pain reduction
In a clinical study by Holdcroft et al., post-operative pain was shown to be reduced by oral cannabis extract.19
In a randomized, double-blinded, placebo-controlled trial by Almog et al., the pharmacokinetics, analgesic properties, cognitive performance, and safety effects of cannabis inhaler (THC: 0.5mg, 1mg) were assessed in 27 people with chronic pain . It was found that pain intensity was significantly reduced by both doses compared with the control group, highlighting that THC exhibits analgesic effects. Mostly mild adverse events were found and non-severe. Also, there was no evidence that cognitive performance was consistently impaired.20
- https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=9218
- https://www.verywellhealth.com/pain-assessment-1131968
- https://www.healthline.com/health/pain
- https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=9218
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/
- https://ghmedical.com/endocannabinoid-system/diseases/pain
- Chen, R., Et al., (2011). “Monoacylglycerol lipase is a therapeutic target for Alzheimer’s disease”. https://doi.org/10.1016/j.celrep.2012.09.030
- Kohnz, R., Et al., (2014). “Chemical approaches to therapeutically target the metabolism and signaling of the endocannabinoid 2-AG and eicosanoids”. https://doi.org/10.1039/c4cs00047a
- Mulvhill, M.M., Et al., (2013). ”Therapeutic Potential of Monoacylglycerol Lipase Inhibitors”. https://doi.org/10.1016/j.lfs.2012.10.025
- Bertolini, A., Et al., (2006). “Paracetamol: new vistas of an old drug”. https://pubmed.ncbi.nlm.nih.gov/17227290/
- Fowler, C.J., Et al., (1999). ” Inhibition of anandamide hydrolysis by the enantiomers of ibuprofen, ketorolac, and flurbiprofen”. https://pubmed.ncbi.nlm.nih.gov/9989926/
- Reche, I., Et al, (1998). “Inhibition of opioid-degrading enzymes potentiates delta9-tetrahydrocannabinol-induced antinociception in mice”. https://pubmed.ncbi.nlm.nih.gov/9680246/
- Bagüés, A., Et al., (2014). “Involvement of central and peripheral cannabinoid receptors on antinociceptive effect of tetrahydrocannabinol in muscle pain”. https://europepmc.org/article/med/25446925
- Murineddu, G., Et al., (2012). “A survey of recent patents on CB2 agonists in the management of pain”. https://pubmed.ncbi.nlm.nih.gov/22280338/
- De Petrocellis, L., Et al., (2011). ” Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes”. https://pubmed.ncbi.nlm.nih.gov/21175579/
- De Petrocellis, L., Et al., (2012). ” Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation”. https://pubmed.ncbi.nlm.nih.gov/21726418/
- Chafouri, B., Et al. (2013). ”Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity”. https://pubmed.ncbi.nlm.nih.gov/23707281/
- Deliu, E., (2015). “The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueductal Gray”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518086/
- Paudel, K.S., Et al., (2010). ” Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers”. https://pubmed.ncbi.nlm.nih.gov/20545522/
- Holdcroft, A., Et al., (2006). “A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management”. https://pubmed.ncbi.nlm.nih.gov/16645457/
- Almog, S., Et al., (2020). “The pharmacokinetics, efficacy, and safety of a novel selective‐dose cannabis inhaler in patients with chronic pain: A randomized, double‐blinded, placebo‐controlled trial”. https://onlinelibrary.wiley.com/doi/full/10.1002/ejp.1605
CANNABINOIDS & RECEPTORS
Below you find the plant cannabinoids, cannabinoid receptors, and endocannabinoids that are associated with the potential therapy.
If you have any further information relevant to the connection between Pain and cannabinoids or find any of the information inaccurate, outdated or incomplete please contact us here.
