Hempsi Pain Topical Cream: CBD studies on pain relief

Before we delve into the biochemical inspirations behind the Hempsi Pain Topical formula, let’s take a minute to emphasize that this product is not intended to treat or cure any diseases. Hempsi Pain Topical has not been approved by the FDA for anything. While the scientific research that inspired this formula is fascinating, it is for educational purposes only. Nothing in this article should be taken as proof of efficacy, or anything other than inspiration behind a work of art that is to be enjoyed. We do not claim that Hempsi Pain Topical will work for you for anything. Our hope is that you’ll try our product, enjoy it, and be inspired too.

Pharmacological Mechanism

  • CBN: CB1/CB2, endocannabinoids, TRP channels, PPAR Gamma  
  • Live Resin - CBD: 5HT,  TRP channels, endocannabinoids, PPAR Gamma, COX
  • Entourage effect
  • PEA: endocannabinoids, PPARa
  • Ecdysterone: ERb, NF-kB, Ribosomes, PI3k/Akt/mTOR
  • MSM: NF-kB, antioxidant, methyl donor
  • Vitamin E: antioxidant
  • Menthol: TRPM8, TRPA, Na channels, Ca channels
  • Thymol: TRPM8, TRPA, Na channels, Ca channels, antioxidant, COX
  • Eucalyptol: TRPM8, TRPA, Na channels, Ca channels, anti-inflammatory
  • Eugenol: TRPV, Na channels, antioxidant, COX, LOX, 
  • Mace: endocannabinoids
  • Caryophyllene: CB2
  • Humulene: CB1
  • Geraniol: Kv1.3 ion channel, Ca channels, K channels, PI3k/Akt/mTOR

Pain perception begins with the stimulation of pain sensing neurons. This can be from any number of causes, whether it’s harmless chemical activation (think of spicy peppers) to direct damage to the tissues of an affected area, or excessive inflammation. It follows that pain can be addressed either by targeting the activation of pain sensing neurons, or by interfering with the signal being sent to the brain. Hempsi’s pain topical uses a multipronged approach to tackle pain through both paths.

On the inflammatory side of things, cannabinoids like CBD activate the nuclear receptor PPAR Gamma1. This “metabolic master switch” governs many cellular processes, and its activation has been shown to reduce the activity of pro-inflammatory immune cells. Among other things, PPAR gamma activation indirectly raises the threshold needed to activate another nuclear receptor, NF-kB2. NF-kB is like an “inflammatory master switch”, which when activated triggers immune activity and the production of various pro-inflammatory signaling molecules. By making NF-kB more difficult to activate, a “road block” is placed in the way of the feedback cycle that is inflammation, preventing it from getting carried away. Ingredients like ecdysterone and MSM inhibit NF-kB more directly3,4, further reducing the level of its activation and thereby suppressing the “start” signal in the inflammatory process.

Cannabinoids also address inflammation through cannabinoid receptors. These receptors are present in many tissues, and their activation has a number of tissue specific functions. In immune mediating tissues (like white blood cells), cannabinoid receptor activation reduces overall activity (through receptor mediated inhibition of adenylate cyclase)5, and tends to guide action away from inflammatory processes. While CB2 is the primary cannabinoid receptor on immune cells, CB1 is also present and important, though more so in many of the tissues being affected by inflammation than in pro-inflammatory immune cells6. CBN, Humulene and Caryophyllene all activate CB1, CB2 or both7,8,9. Furthermore, cannabinoids like CBN and CBD increase the available concentration of the body’s own version of cannabinoids (endocannabinoids)10, which also act on both CB1 and CB2. This property is shared by PEA (Palmitoylethanolamide)11 and components of Mace/Nutmeg essential oil12

A third means through which cannabinoids can inhibit inflammatory processes is through inhibition of enzymes that mediate steps in the inflammatory feedback cycle. Like ibuprofen, cannabinoids like CBD inhibit COX (cyclooxygenase) enzymes13, which produce several inflammatory signaling molecules. This property is shared with the terpenoids thymol and eugenol14,15, which also inhibits similar LOX (lipoxygenase) enzymes16. By reducing the amount of the inflammatory mediators being produced by these enzymes, these ingredients put yet another roadblock in the inflammatory feedback pathway.   

Oxidative stress is another fundamental part of inflammation. Active inflammatory immune cells generate extremely reactive molecules known as free radicals that serve several functions, including cell signaling and destruction of pathogens and or toxins. These radicals can damage tissues when produced in excess or are otherwise uncontrolled, and directly activate pain sensing neurons through receptors like TRPA (responsible for spiciness from horseradish). By reducing the number of radicals available to damage tissues and  interact with receptors like TRPA, activation of pain sensing neurons is reduced. Many of the ingredients in Hempsi Pain Topical “scavenge”  radicals and thereby function as antioxidants. All cannabinoids studied, for instance, scavenge radicals17, as do most terpenes18 as well as MSM19. MSM, vitamin E, thymol and eugenol are particularly effective in this regard20, 21, 22, so much so that they are also used to extend the shelflife of the product. 

In addition to radical scavenging properties, many terpenoids act on ion channels in cell membranes that regulate the cell’s function in various ways. Of particular importance for inflammation is the voltage gated potassium channel Kv1.3, which is inhibited by the terpenoid geraniol23. This mechanism reduces the production of pro-inflammatory cytokines by immune cells, thereby suppressing the inflammatory process. Geraniol also activates the PI3k/Akt/mTOR intracellular signaling pathway in affected tissues24. This anabolic pathway encourages recycling of old cellular structures and stimulates the synthesis of new ones, building tissues back up from damage. This property is shared with ecdysterone, which also stimulates protein synthesis by increasing translational and transcriptional efficiency as well as the expression of genes associated with anabolic processes25.

On the neurological side of things, cannabinoids (and endocannabinoids) are again the star of the show. Activation of CB1 (and to a lesser extent CB2) in pain sensing neurons reduces their overall activity through G-protein mediated inhibition of adenylate cyclase26. This makes pain sensing neurons less sensitive to stimulus in general. Cannabinoids, endocannabinoids and several terpenoids also interact with TRP channels27. These ligand gated ion channels are expressed on pain sensing neurons, and their activation is the initial trigger for sending a pain signal. Neurons respond to the stimulation of TRP channels by cannabinoids and other ligands by reducing their responsiveness to activating stimuli as well as by reducing the number of receptors being expressed28. This means that these TRP activating compounds further reduce the pain sensing neuron’s sensitivity to stimulation. 

Several terpenoids, like eugenol and thymol, also inhibit voltage gated sodium and calcium channels29, 30. Voltage gated sodium channels are responsible for propagating electric signals down the body of a neuron, while voltage gated calcium channels are responsible for converting the electric signal into a biochemical response in the cell(s). By interfering with these processes, terpenoids like eugenol and thymol reduce a pain sensing neuron’s ability to transmit signals to the brain, so much so that they can even cause a numbing sensation in high concentrations. Eugenol specifically is often used in medical settings as a local anesthetic because of its numbing effect31.

CBD may directly affect pain neuron sensitivity by mimicking serotonin at type 1 inhibitory serotonin receptors (5HT1a)32. These receptors play a starring role in establishing “neural fatigue”. Like cannabinoid receptors, 5HT1a is g-protein coupled and directly inhibits the enzyme adenylate cyclase, thereby reducing cellular activity in general. 5HT1a is expressed on the long “bodies” of neurons as well as in the synapse (where neurons meet)33. These “extrasynaptic” receptors detect the “spill over” of serotonin that follows excessive neural activity and neurotransmitter release. By mimicking serotonin at these receptors, CBD triggers this negative feedback process, thereby reducing neural activity. In pain sensing neurons, this results in a reduced sensitivity to stimulus and a reduced magnitude of signal being sent when the neuron is activated. 

Last but not least, the protective and  tissue-building PI3k/Akt/mTOR mechanism exhibited by geraniol and ecdysterone takes place in neurons in addition to the previously mentioned tissues. This helps to prevent damage to pain sensing nerves and the excessive activity that follows34. This is complemented by CB1 mechanisms in neurons, where ligand bias/protean agonism may cause activation of the same PI3k/Akt/mTOR pathway35 initiated by geraniol and ecdysterone, albeit from a different trigger. Reduced neural activity along with activated PI3k/Akt/mTOR protects pain sensing neurons from injury and damage, helping to prevent neural inflammation that is itself a cause of pain. 

Absorption Mechanism

  • Glycerine Hydrate skin, “open gate” (Hydrophilic absorption)
  • Laurocapram/Azone fluidizing cell junction components, “open front door” (hydrophobic absorption)
  • PG, oleic, menthol et al. between cell junctions, “hold the door” (Hydrophobic absorption)
  • DMI  and oleic, eucalyptol,  carries active ingredients through junctions, “usher down the hallway” (Both)
  • MSM behaves similarly to DMSO (pour formation), “sneak through the window/chimney/vents, etc.” (Hydrophilic absorption)

Hempsi Pain Topical is a unique emulsion designed for maximum dermal absorption. An anhydrous (without water) glycerol/propylene glycol solution containing the hydrophilic (water-soluble) active ingredients is mixed in equal parts with an oil-based solution containing the hydrophobic (oil-soluble) ingredients. Since the polar phase is anhydrous, the two phases are “semi-miscible”. The resulting mixture doesn’t show distinct separation, but some transient partitioning is apparent. Ingredients dissolved in either phase have varying degrees of solubility in both phases, and so can be absorbed all together through cooperating hydrophobic and hydrophilic mechanisms. This mixture is then combined with several excipients to control texture and improve stability, which are emulsified in the more traditional sense to achieve the final material.

The strategy for dermal penetration comes in several parts. First, glycerol in the formula hydrates the skin36. Glycerol does so directly, but being hygroscopic, also draws water into the skin for further hydration. The fully hydrated tissue of the epidermis accepts the formula, providing access to dermis. Here, glycerol and propylene glycol interact with cell membranes and slightly increase their permeability37. This sets the stage for MSM (methylsulfonylmethane) to interact with proteins in the cell membranes in such a way as to create channels for small molecules to pass through in a manner very similar to its cousin DMSO (Dimethylsulfoxide)38. This grants other hydrophilic active ingredients access to intracellular pharmacological targets, such as nuclear receptors. These hydrophilic mechanisms are aided by DMI’s (Dimethyl Isosorbide) ability to partially dissolve in oils, essentially carrying hydrophilic portions of the formula past minor hydrophobic barriers like in the tissue of the epidermis (Stratum Corneum)39

DMI’s unique properties also mean that it helps to usher hydrophobic ingredients to their targets. DMI helps to give the terpenoid and alcohol ingredients in the formula (like geraniol and propylene glycol, as well as several others) access to the junctions between cells in the dermis (and other tissues). Laurocapram “fluidizes” these cell junctions40, allowing small molecules to more easily enter the space between cells. Here, the hydrophobic nature of terpenoids and alcohols allows them to enter the lipid based junction, where they become somewhat “stuck”41, 42, essentially holding the junction open just a little bit. This allows more of these components of the formula to get just a little bit farther through the junction, where they do the same thing. All of this aids oleic acid, eucalyptol and DMI in passing through the cell junctions43, 44, 45, to reach the next tissue layer while carrying the formula’s active ingredients. By “opening all the doors” of the skin barrier just a little bit, this formula is able to carry its active ingredients to the real sources of pain, deep in tissues. 

Thickeners and other excipients in the formula give it a pleasant texture, as well as hold it against the skin. All this absorption takes time, even when it’s rubbed in. Approximately 5 minutes after application, you will notice a pleasurable heating/cooling, tingling sensation on the applied area. This sensation becomes stronger and deeper over time, soon soothing even deep aches and pains. 

Active Ingredients:

  • Menthol
  • Thymol
  • Eucalyptol
  • Eugenol

Supporting Ingredients

  • Ecdysterone 95% by UV             
  • (Cyanotis Arachnoidea Extract)
  • Methylsulfonylmethane (MSM) 
  • Palmitoylethanolamide (PEA) 
  • Cannabinoids (CBN, Decarbed Live Resin) 
  • Vitamin E
  • Mace (Nutmeg)
  • Caryophyllene
  • Humulene
  • Geraniol
  • Penetration Enhancers
  • Menthol et al
  • MSM
  • Dimethyl Isosorbide (DMI)
  • Laurocapram
  • Oleic Acid
  • Glycerine
  • Propylene Glycol
  • Excipients
  • Hydroxypropylcellulose - thickener/ film former
  • Glyceryl Monostearate - thickener/emulsifier/ film former
  • Cetearyl Alcohol - thickener
  • Quillaja Saponins - emulsifier


  1.  O'Sullivan S. E. (2016). An update on PPAR activation by cannabinoids. British journal of pharmacology, 173(12), 1899–1910. https://doi.org/10.1111/bph.13497 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882496/ 
  2.  Korbecki, J., Bobiński, R. & Dutka, M. Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflamm. Res. 68, 443–458 (2019). https://doi.org/10.1007/s00011-019-01231-1 https://link.springer.com/article/10.1007/s00011-019-01231-1 
  3.  Feng CY, Huang XR, Qi MX. [Effects of ecdysterone on the expression of NF-kappaB p65 in H2O2 induced oxidative damage of human lens epithelial cells]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Jan;32(1):76-9. Chinese. PMID: 22500399. https://pubmed.ncbi.nlm.nih.gov/24648308/ 
  4. Joung YH, Darvin P, Kang DY, SP N, Byun HJ, Lee C-H, et al. (2016) Methylsulfonylmethane Inhibits RANKL-Induced Osteoclastogenesis in BMMs by Suppressing NF-κB and STAT3 Activities. PLoS ONE 11(7): e0159891. https://doi.org/10.1371/journal.pone.0159891 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159891 
  5.  Pandey, R., Mousawy, K., Nagarkatti, M., & Nagarkatti, P. (2009). Endocannabinoids and immune regulation. Pharmacological research, 60(2), 85–92. https://doi.org/10.1016/j.phrs.2009.03.019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044336/ 
  6.  Resat Cinar, Malliga R. Iyer, George Kunos, The therapeutic potential of second and third generation CB1R antagonists, Pharmacology & Therapeutics, Volume 208, 2020, 107477, ISSN 0163-7258, https://doi.org/10.1016/j.pharmthera.2020.107477. (https://www.sciencedirect.com/science/article/pii/S016372582030005X
  7. Morales, P., Hurst, D. P., & Reggio, P. H. (2017). Molecular Targets of the Phytocannabinoids: A Complex Picture. Progress in the chemistry of organic natural products, 103, 103–131. https://doi.org/10.1007/978-3-319-45541-9_4  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/pdf/nihms849724.pdf 
  8.  LaVigne, J.E., Hecksel, R., Keresztes, A. et al. Cannabis sativa terpenes are cannabimimetic and selectively enhance cannabinoid activity. Sci Rep 11, 8232 (2021). https://doi.org/10.1038/s41598-021-87740-8 https://www.nature.com/articles/s41598-021-87740-8 
  9.  Aly, E., Khajah, M. A., & Masocha, W. (2019). β-Caryophyllene, a CB2-Receptor-Selective Phytocannabinoid, Suppresses Mechanical Allodynia in a Mouse Model of Antiretroviral-Induced Neuropathic Pain. Molecules (Basel, Switzerland), 25(1), 106. https://doi.org/10.3390/molecules25010106 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983198/ 
  10.  De Petrocellis, L., Ligresti, A., Moriello, A. S., Allarà, M., Bisogno, T., Petrosino, S., Stott, C. G., & Di Marzo, V. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British journal of pharmacology, 163(7), 1479–1494. https://doi.org/10.1111/j.1476-5381.2010.01166.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165957/ 
  11.  Di Marzo, V., Melck, D., Orlando, P., Bisogno, T., Zagoory, O., Bifulco, M., Vogel, Z., & De Petrocellis, L. (2001). Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells. The Biochemical journal, 358(Pt 1), 249–255. https://doi.org/10.1042/0264-6021:3580249 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222054/ 
  12.  El-Alfy AT, Joseph S, Brahmbhatt A, Akati S, Abourashed EA. Indirect modulation of the endocannabinoid system by specific fractions of nutmeg total extract. Pharm Biol. 2016 Dec;54(12):2933-2938. doi: 10.1080/13880209.2016.1194864. Epub 2016 Jun 14. PMID: 27296774. https://pubmed.ncbi.nlm.nih.gov/27296774/ 
  13.   Ruhaak LR, Felth J, Karlsson PC, Rafter JJ, Verpoorte R, Bohlin L. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011;34(5):774-8. doi: 10.1248/bpb.34.774. PMID: 21532172. https://pubmed.ncbi.nlm.nih.gov/21532172/ 
  14.  Marsik P, Kokoska L, Landa P, Nepovim A, Soudek P, Vanek T. In vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosyntheses. Planta Med. 2005 Aug;71(8):739-42. doi: 10.1055/s-2005-871288. PMID: 16142638. https://pubmed.ncbi.nlm.nih.gov/16142638/ 
  15.  Ya-Yun Lee, Shan-Ling Hung, Sheng-Fang Pai, Yuan-Ho Lee, Shue-Fen Yang, Eugenol Suppressed the Expression of Lipopolysaccharide-induced Proinflammatory Mediators in Human Macrophages, Journal of Endodontics, Volume 33, Issue 6, 2007, Pages 698-702, ISSN 0099-2399, https://doi.org/10.1016/j.joen.2007.02.010. (https://www.sciencedirect.com/science/article/pii/S0099239907001665
  16. das Chagas Pereira de Andrade, F., Mendes, A.N. Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways. Sci Rep 10, 16204 (2020). https://doi.org/10.1038/s41598-020-73203-z https://www.nature.com/articles/s41598-020-73203-z 
  17.  Andrzej L. Dawidowicz, Małgorzata Olszowy-Tomczyk, Rafał Typek, CBG, CBD, Δ9-THC, CBN, CBGA, CBDA and Δ9-THCA as antioxidant agents and their intervention abilities in antioxidant action, Fitoterapia, Volume 152, 2021, 104915, ISSN 0367-326X, https://doi.org/10.1016/j.fitote.2021.104915. (https://www.sciencedirect.com/science/article/pii/S0367326X21000903
  18. Bechir Baccouri and Imen Rajhi (July 28th 2021). Potential Antioxidant Activity of Terpenes, Terpenes and Terpenoids - Recent Advances, Shagufta Perveen and Areej Mohammad Al-Taweel, IntechOpen, DOI: 10.5772/intechopen.96638. Available from: https://www.intechopen.com/chapters/75827 
  19.  Butawan, M., Benjamin, R. L., & Bloomer, R. J. (2017). Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients, 9(3), 290. https://doi.org/10.3390/nu9030290 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372953/ 
  20.   Duval C, Poelman MC. Scavenger effect of vitamin E and derivatives on free radicals generated by photoirradiated pheomelanin. J Pharm Sci. 1995 Jan;84(1):107-10. doi: 10.1002/jps.2600840124. PMID: 7714730. https://pubmed.ncbi.nlm.nih.gov/7714730/ 
  21.  Jamali, T., Kavoosi, G., Jamali, Y. et al. In-vitro, in-vivo, and in-silico assessment of radical scavenging and cytotoxic activities of Oliveria decumbens essential oil and its main components. Sci Rep 11, 14281 (2021). https://doi.org/10.1038/s41598-021-93535-8 https://www.nature.com/articles/s41598-021-93535-8 
  22.  Gülçin İ. Antioxidant activity of eugenol: a structure-activity relationship study. J Med Food. 2011 Sep;14(9):975-85. doi: 10.1089/jmf.2010.0197. Epub 2011 May 9. PMID: 21554120. https://pubmed.ncbi.nlm.nih.gov/21554120/ 
  23.  Ye CJ, Li SA, Zhang Y, Lee WH. Geraniol targets KV1.3 ion channel and exhibits anti-inflammatory activity in vitro and in vivo. Fitoterapia. 2019 Nov;139:104394. doi: 10.1016/j.fitote.2019.104394. Epub 2019 Oct 25. PMID: 31669719. https://pubmed.ncbi.nlm.nih.gov/31669719/ 
  24.  Younis NS, Abduldaium MS, Mohamed ME. Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways. Antioxidants. 2020; 9(10):977. https://doi.org/10.3390/antiox9100977 https://www.mdpi.com/2076-3921/9/10/977/htm 
  25.  Dinan L, Dioh W, Veillet S, Lafont R. 20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases. Biomedicines. 2021; 9(5):492. https://doi.org/10.3390/biomedicines9050492 https://www.mdpi.com/2227-9059/9/5/492/htm 
  26.  Manzanares, J., Julian, M., & Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Current neuropharmacology, 4(3), 239–257. https://doi.org/10.2174/157015906778019527 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/ 
  27.  Janero, D. R., & Makriyannis, A. (2014). Terpenes and lipids of the endocannabinoid and transient-receptor-potential-channel biosignaling systems. ACS chemical neuroscience, 5(11), 1097–1106. https://doi.org/10.1021/cn5000875 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948289/ 
  28.  Muller, C., Morales, P., & Reggio, P. H. (2019). Cannabinoid Ligands Targeting TRP Channels. Frontiers in molecular neuroscience, 11, 487. https://doi.org/10.3389/fnmol.2018.00487 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340993/ 
  29.  Huang CW, Chow JC, Tsai JJ, Wu SN. Characterizing the effects of Eugenol on neuronal ionic currents and hyperexcitability. Psychopharmacology (Berl). 2012 Jun;221(4):575-87. doi: 10.1007/s00213-011-2603-y. Epub 2011 Dec 13. PMID: 22160139. https://pubmed.ncbi.nlm.nih.gov/22160139/ 
  30.  Nagoor Meeran MF, Javed H, Al Taee H, Azimullah S, Ojha SK. Pharmacological Properties and Molecular Mechanisms of Thymol: Prospects for Its Therapeutic Potential and Pharmaceutical Development. Front Pharmacol. 2017 Jun 26;8:380. doi: 10.3389/fphar.2017.00380. PMID: 28694777; PMCID: PMC5483461. https://pubmed.ncbi.nlm.nih.gov/28694777/ 
  31.  Park CK, Kim K, Jung SJ, Kim MJ, Ahn DK, Hong SD, Kim JS, Oh SB. Molecular mechanism for local anesthetic action of eugenol in the rat trigeminal system. Pain. 2009 Jul;144(1-2):84-94. doi: 10.1016/j.pain.2009.03.016. Epub 2009 Apr 18. PMID: 19376653. https://pubmed.ncbi.nlm.nih.gov/19376653/ 
  32.  Russo, E.B., Burnett, A., Hall, B. et al. Agonistic Properties of Cannabidiol at 5-HT1a Receptors. Neurochem Res 30, 1037–1043 (2005). https://doi.org/10.1007/s11064-005-6978-1 https://link.springer.com/article/10.1007/s11064-005-6978-1 
  33.  Loyd, D. R., Henry, M. A., & Hargreaves, K. M. (2013). Serotonergic neuromodulation of peripheral nociceptors. Seminars in cell & developmental biology, 24(1), 51–57. https://doi.org/10.1016/j.semcdb.2012.09.002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104492/ 
  34.  Li, R., Li, Dh., Zhang, Hy. et al. Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration. Acta Pharmacol Sin 41, 1289–1300 (2020). https://doi.org/10.1038/s41401-019-0338-1 https://www.nature.com/articles/s41401-019-0338-1 
  35.   Giacoppo S, Pollastro F, Grassi G, Bramanti P, Mazzon E. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis. Fitoterapia. 2017 Jan;116:77-84. doi: 10.1016/j.fitote.2016.11.010. Epub 2016 Nov 25. PMID: 27890794. http://www.orvosikannabisz.com/wp-content/uploads/2016/11/giacoppo2017.pdf 
  36.  Yamada, T., Habuka, A. and Hatta, I. (2021), Moisturizing mechanism of glycerol and diglycerol on human stratum corneum studied by synchrotron X-ray diffraction. Int. J. Cosmet. Sci., 43: 38-47. https://doi.org/10.1111/ics.12664 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ics.12664 
  37.  Min Zhang, Ira G. Wong, Jerry B. Gin & Naseem H. Ansari (2009) Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy, Drug Delivery, 16:5, 243-248, DOI: 10.1080/10717540902896362 https://www.tandfonline.com/doi/full/10.1080/10717540902896362?scroll=top&needAccess=true 
  38.  Kushwaha, Abhishek. (2018). A Screening of Permeation Enhancers for Transdermal Delivery of Propofol. Journal of Bioequivalence & Bioavailability. 10. 10.4172/0975-0851.1000378.  https://www.longdom.org/open-access/a-screening-of-permeation-enhancers-for-transdermal-delivery-of-propofol-0975-0851-1000378.pdf 
  39.  López-Cervantes, Miriam & Márquez-Mejía, Eréndira & C. D., Jennyfer & Quintanar, David & Ganem, Adriana. (2006). Chemical Enhancers for the Absorption of Substances Through the Skin: Laurocapram and Its Derivatives. Drug development and industrial pharmacy. 32. 267-86. 10.1080/03639040500518708.  https://www.researchgate.net/publication/7221868_Chemical_Enhancers_for_the_Absorption_of_Substances_Through_the_Skin_Laurocapram_and_Its_Derivatives 
  40.  Kunta JR, Goskonda VR, Brotherton HO, Khan MA, Reddy IK. Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J Pharm Sci. 1997 Dec;86(12):1369-73. doi: 10.1021/js970161+. PMID: 9423148. https://pubmed.ncbi.nlm.nih.gov/9423148/