Pain, by definition, is described as mental or physical suffering. Different receptors register different events and essentially convey to the brain if the experience is to be deemed painful or not. The peripheral nerves run throughout your body and send signals from nerve endings to the central nervous systems to register pain as well as other sensations. In addition to registering pain, the peripheral nerves also have been shown to have cannabinoid receptor type 1 and cannabinoid receptor type 2; both found to be to vital in analgesia. This article reviews the literature to examine the analgesic properties of cannabis. In the first section we focus on studies and recorded observations on medicinal cannabis for pain relief mainly based in the 19th century. As the second and third sections unfold, we transition to more recent studies up until the 21st century, as well as what direction we are currently headed in. We close out by discussing the way cannabinoids alleviate pain by binding to the peripheral and central nerves based on current studies.
When we think of cannabis many conflicting thoughts tend to come to mind, such as it’s an illicit drug and yet has been used in the medical field since its discovery. From movies such as Reefer Madness to being labeled as a “gateway drug,” cannabis has gained a negative connotation over the years despite its many health benefits. The first case of cannabis being used in a pharmaceutical manner can be traced back to 2737 B.C. when Chinese emperor Shen Neng began to prescribe cannabis to treat illnesses such as gout, beriberi, and rheumatism. If we fast forward to the 21st century and examine studies, we will see that cannabidiol (CBD) oil has been studied for its benefits in treating rheumatoid arthritis. There have been many writings on cannabis in general found in the B.C. era in China. Though it is not mentioned in abundance, there is evidence that early Chinese cultures used cannabis for medicinal purposes, but they did in fact know about its psychotropic properties. It has been noted (1) that if used for a prolonged time, cannabis would produce different hallucinogenic effects but, with the decline in shamanism in the Han Dynasty, the use of cannabis as a hallucinogen fell out of practice. Many cultures spoke of using cannabis in a lot of different medicinal forms whether it was the Assyrians using it as a cure for swelling and bruises or the Greeks using “juice” from the cannabis seeds as a cure for earaches (2).
As time progressed, there was never a clear decrease in cannabis use in medicinal purposes. By the start of the 19th century there was a sharp rise in studies on the medicinal benefits of cannabis, especially in western civilization. In 1843, William Brooke O’Shaughnessy introduced his findings from India detailing how different cannabis tinctures were made in India as well as the effects these tinctures had on each patient (3).
Medicinal Cannabis in the 19th Century
O’Shaughnessy begins with his description of tests run on animals in the beginning; the first of which being done on a medium sized dog. In this early cohort study, O’Shaughnessy was simply observing the effects of a tincture made of 10 grains of ”Nipalese churrus” dissolved in a spirit (3). The effects of the tincture were described as giving the dog a “stupid” state followed by hunger and a long slumber; throughout the whole ordeal the dog was described as very content. Similar reactions were found as tests were continued on dogs. Deeper into O’Shaughnessy’s article he gives examples of patients whom had acute rheumatism; all of whom had not been responding to conventional methods of treatment. Though one patient had adverse effects where they fell into a catalepsy state; all patients with the exception of the habitual cannabis user stated loss of pain associated with the acute rheumatism. One patient even described himself as ”being in perfect health” after taking one grain of resin; while one of the other patients exclaimed he was free of all symptoms after taking the tincture and having a full night’s rest. O’Shaughnessy was able to observe several more cases in which the half-grain dose of cannabis resin was used as treatment in acute and chronic rheumatism; across the board it was shown that the resin was able to attenuate the pain.
In 1845 Mr. M. Donovan began to do his own experimentation of Indian cannabis, which was the main source for O’Shaughnessy’s experiments. Donovan’s interest in the subject matter stemmed from his own suffering of neuralgic pain (4). In his early attempts, Donovan found no effects after making his own resin and tincture by using Indian hemp that he obtained from various sources. He deemed the reason for his tincture and resin not being as potent as O’Shaughnessy’s because of poor cultivation techniques as well as the possibility that the cannabis loses its potency after being cut and thus has a finite time in which it can be used and still produce the desired effects. This issue was eradicated by obtaining fresh resin samples made by O’Shaughnessy himself. During one of his pain attacks Donovan took the tincture made from O’Shaughnessy’s resin and in 20 min he described himself as having no pain whatsoever. He also described a feeling of moving around without giving thought to his legs to the point that he felt as if “they (his legs) did not belong to me” (4). It can be observed through Donovan’s account that as time went on, he had to take higher doses of tincture in order to alleviate his pain.
In an article published in The Lancet in March 1890, one man by the alias W.W. gives his own account of the adverse effect of taking a cannabis tincture. He description goes as follows (5):
“The neuralgia, was soon forgotten, and in about an hour’s time I began to feel giddy, full in the head, and very faint, and soon experienced a sensation of heaviness and numbness in the feet and legs, followed by partial anesthesia, gradually extending upwards to the knees. My feet and legs felt as if enormously swollen and thickly covered over with wool. Soon the loss of sensation became complete as far as the knees; walking was then impossible and even standing a difficulty. Shortly similar symptoms appeared in the upper extremities, commencing at the finger tips and extending as far as the elbows. The anesthesia was not so complete as in the lower extremities. During this time there was great anxiety and fear of death through cardiac paralysis, which seemed almost imminent. The heart’s action was tumultuous and irregular. On the return of sensation to the extremities, I was possessed with an almost irresistible desire to commit suicide, by rushing into the adjoining canal or cutting my throat with the knives on the table close by, though no attempt was made at doing so. Shortly upon this I was seized with fits of alternate laughter and crying, without any apparent cause.”
W.W. ended the article stating he was aware that cannabis tinctures don’t affect everybody the same way, but that he would never take it as a cure again as well as “be most careful in prescribing it to others.” In a turn of events Dr. J.R. Reynolds gave a retort to W.W.’s article seven days later. In his article, Dr. Reynolds explained why one might succumb to toxic symptoms after taking a cannabis tincture. Dr. Reynolds’ explained the symptoms related to the tincture not being made homogenous in addition to different cannabis resin being extracted from different strands grown in different regions. He concluded that to combat against this the cannabis should be obtained from the same source and users should start with the lowest possible dosage before ramping up in attempts to test the potency of the tincture made and gradually increased from there (5). Dr. Reynolds also gave a list of steps to take when taking a tincture of the pharmacopoeia and assured readers that in all his studies, when subjects followed his method for dosing, no one experienced an adverse effect.
- M. Touwn, J. Psychoactive Drugs. 13(1), 23–34 (1981).
- A.W. Zuardi, Brazilian Journal of Psychiatry 28(2), 153–157, doi:10.1590/s1516-44462006000200015 (2006).
- W.B. O’Shaughnessy, Provisional Medical Journal Feb. 4, 1843, 336–339.
- M. Donovan, The Dublin Journal of Medical Science 26(3), 368–402, doi:10.1007/bf02971741 (1845).
- W.W., The Lancet 135(3472), 621, doi:10.1016/s0140-6736(02)15560-7 (1890).
- R. Noyes, F.S. Brunk, D.H. Avery, and A. Canter, Clin. Pharmacol. Ther. 18(1), 84–89, doi:10.1002/cpt197518184 (1975).
- S. Milstein, K. MacCannell, G. Karr, and S. Clark, Int. Pharmacopsychiatry 10(3), 177–182, doi:10.1159/000468188 (1975).
- D.I. Abrams, C.A. Jay, S.B. Shade, H. Vizoso, H. Reda, S. Press, and K.L. Petersen, Neurology 68(7), 515–521, doi: 10.1212/01.wnl.0000253187.66183.9c (2007).
- M.A. Ware, C.R. Doyle, R. Woods, M.E. Lynch, and A.J. Clark, Pain 102(1), 211–216, doi:10.1016/s0304-3959(02)00400-1 (2003).
- M.A. Ware, T. Wang, S. Shapiro, A. Robinson, T. Ducruet, T. Huynh, and J. Collet, Can. Med. Assoc. J. 182(14), doi:10.1503/cmaj.091414 (2010).
- Controlled Substances (PDF). (2018, October 01). Drug Enforcement Agency.
- B.E. Perron, K.R. Holt, E. Yeagley, and M. Ilgen, Drug Alcohol Depend. 194, 401–409, doi: 10.1016/j.drugalcdep.2018.09.029 (2018).
- United States, Bureau of Cannabis Control, State of California. (2018, June). Bureau of Cannabis Control Text of Regulations. Retrieved from https://bcc.ca.gov/law_regs/readopt_text_final.pdf.
- A. Calignano, G.L. Rana, A. Giuffrida, and D. Piomelli, Nature 394(6690), 277–281, doi:10.1038/28393 (1998).
- A. Hama and J. Sagen, Brain Research 1412, 44–54, doi:10.1016/j.brainres.2011.07.031 (2011).
- J.D. Richardson, S. Kilo, and K.M. Hargreaves, Pain 75(1), 111–119, doi:10.1016/s0304-3959(97)00213-3 (1998).
- K.T. Brady and R.L. Balster, Psychopharmacology 72(1), 21–26, doi:10.1007/bf00433803 (1980).
- N. Clayton, F.H. Marshall, C. Bountra, and C.T. O’Shaughnessy, Pain 96(3), 253–260, doi:10.1016/s0304-3959(01)00454-7 (2002).
- R. Mechoulam and L. Parker, Br. J. Pharmacol. 170(7), 1363–1364, doi:10.1111/bph.12400 (2013).
- E. Russo, Therapeutics and Clinical Risk Management 4, 245–259, doi:10.2147/tcrm.s1928 (2008).
- E.J. Rahn, A. Makriyannis, and A.G. Hohmann, Br. J. Pharmacol. 152(5), 765–777, doi:10.1038/sj.bjp.0707333 (2007).
- G. Muccioli and D. Lambert, Curr. Med. Chem. 12(12), 1361–1394, doi:10.2174/0929867054020891 (2005).
- J.D. Vry, K.R. Jentzsch, E. Kuhl, and G. Eckel, Behav. Pharmacol. 15(1), 1–12, doi:10.1097/00008877-200402000-00001 (2004).
- E. Russo and G.W. Guy, Med. Hypotheses 66(2), 234–246, doi:10.1016/j.mehy.2005.08.026 (2006).
- P. Flachenecker, T. Henze, and U.K. Zettl, Eur. Neurol. 71(5–6), 271–279, doi:10.1159/000357427 (2014).
Jamal Bouie is a cannabis chemical analyst based out of Long Beach, California. He is a member of the Long Beach Collective Association (LBCA) as well as the SoCal Cannabis Science Research Group (ScCSRG). Niranjan Aryal is a lab director for a cannabis testing laboratory in the SoCal area. He is also a member of the SoCal Cannabis Group and is continuously looking for ways to complete research within the cannabis field. Direct correspondence to: [email protected]
How to Cite This Article
J. Bouie and N. Aryal, Cannabis Science and Technology 2(5), 62–65 (2019).