Cannabis is a plant native to central and south Asia, used for centuries both medicinally and recreationally, the latter due to its psychoactive effects. The species Cannabis sativa has been researched in MS for decades for apparent benefits against related muscle spasticity1,2, pain, and other discomforts3. 

     The most studied active compounds are d-9-THC, CBD, d-8-THC and cannabinol delta-9-tetrahydrocannabinol (THC), delta-8 THC, cannabidiol (CBD), and cannabinol. While THC was primarily used in the earliest studies, CBD has more recently attracted more attention due to not having the psychoactive effects associated with THC4. An important neurotransmitter system in the body with cannabinoid receptors, called the endocannabinoid system, is widely distributed in the brain, and is considered to be responsible for numerous significant functions5. The endocannabinoid system has been observed to be involved in the control of immune function6 and myelination7.

     Several randomized, placebo-controlled clinical studies found benefits of Cannabis sativa against MS-related spasticity, with tolerable side effects whether smoked8, or through extracted THC and CBD3,9-11. Another study found cannabis to be far superior to placebo in alleviating a related symptom, muscle stiffness12.

     An analysis of anecdotal evidence of THC and CBD against MS-related pain showed the treatment to hold promise13. The relationship with pain was supported by randomized, placebo-controlled clinical studies3,14.

The treatment provided was most often cannabis extract capsules or oromucosal sprays standardized to 2.5-12.7 mg THC and/or 0.9-2.7 mg CBD each (most with), with the dose often increased gradually to up to 120 mg THC per day as tolerated3,10-12,15. Cannabis was generally well tolerated, with side effects including dizziness, dry mouth, somnolence, and lessened long-term memory storage14, without dependence15.

     Of note, not all clinical studies identified benefits with cannabis treatment3,10,15-18, suggesting that its effects may depend somewhat on dosing and individual response.

     Adverse effects of cannabis use during pregnancy have been found in scientific studies19,20. These effects include psychiatric abnormalities such as psychoses in childhood and adolescence19, abnormal fetal blood pressure21, impaired growth22,23, premature labor24, and death23. Even among cannabis-welcoming groups such as midwives who embrace its general use, cannabis during pregnancy is discouraged24.

     THC and CBD are excreted into breastmilk in small quantities, with the duration of detection in milk ranging from six days to greater than six weeks in various studies. There has been concern regarding possible effects of cannabis on neurotransmitters, nervous system development and endocannabinoid-related functions in breastfed infants of mothers using cannabis. Additionally, a preliminary study found a decrease in levels of secretory IgA (SIgA) – a key immunity-building compound – in the milk of cannabis users. No less significant, a one-year study found that daily or near daily cannabis use might retard the breastfed infant’s motor development, though not his/her growth or intellectual development. The latter and another study found that occasional maternal cannabis use during breastfeeding did not have any discernable effects on breastfed infants. However, it should be noted that these studies were inadequate to rule out all long-term harm. Overall, because of insufficient long-term data on the outcome of infants exposed to cannabis via breastmilk, health professionals’ opinions on the acceptability of breastfeeding by cannabis-using mothers varies, though in general, professional guidelines recommend that cannabis use should be avoided by nursing mothers. In addition to possible adverse effects from cannabinoids in breastmilk, paternal cannabis use may also increase the risk of sudden infant death syndrome in infants. It goes without saying that cannabis should not be smoked by anyone in the vicinity of infants, but rather taken though supplements and/or edibles25.

References

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2. Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse. 1987;7(1):39-50. doi:10.1300/j251v07n01_04

3. Wade DT, Makela P, Robson P, House H, Bateman C. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. Aug 2004;10(4):434-41. doi:10.1191/1352458504ms1082oa

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8. Corey-Bloom J, Wolfson T, Gamst A, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. Jul 10 2012;184(10):1143-50. doi:10.1503/cmaj.110837

9. Collin C, Davies P, Mutiboko IK, Ratcliffe S, Sativex Spasticity in MSSG. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. Mar 2007;14(3):290-6. doi:10.1111/j.1468-1331.2006.01639.x

10. Vaney C, Heinzel-Gutenbrunner M, Jobin P, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler. Aug 2004;10(4):417-24. doi:10.1191/1352458504ms1048oa

11. Zajicek JP, Sanders HP, Wright DE, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. Dec 2005;76(12):1664-9. doi:10.1136/jnnp.2005.070136

12. Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG, Group MR. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. Nov 2012;83(11):1125-32. doi:10.1136/jnnp-2012-302468

13. Notcutt W, Price M, Miller R, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 ‘N of 1’ studies. Anaesthesia. May 2004;59(5):440-52. doi:10.1111/j.1365-2044.2004.03674.x

14. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. Sep 27 2005;65(6):812-9. doi:10.1212/01.wnl.0000176753.45410.8b

15. Schimrigk S, Marziniak M, Neubauer C, Kugler EM, Werner G, Abramov-Sommariva D. Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. Eur Neurol. 2017;78(5-6):320-329. doi:10.1159/000481089

16. Centonze D, Mori F, Koch G, et al. Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis. Neurol Sci. Dec 2009;30(6):531-4. doi:10.1007/s10072-009-0136-5

17. Killestein J, Hoogervorst EL, Reif M, et al. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology. May 14 2002;58(9):1404-7. doi:10.1212/wnl.58.9.1404

18. Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. Nov 8 2003;362(9395):1517-26. doi:10.1016/S0140-6736(03)14738-1

19. Frau R, Melis M. Sex-specific susceptibility to psychotic-like states provoked by prenatal THC exposure: Reversal by pregnenolone. J Neuroendocrinol. Feb 2023;35(2):e13240. doi:10.1111/jne.13240

20. Rouzer SK, Gutierrez J, Larin KV, Miranda RC. Alcohol & cannabinoid co-use: Implications for impaired fetal brain development following gestational exposure. Exp Neurol. Mar 2023;361:114318. doi:10.1016/j.expneurol.2023.114318

21. Brar BK, Patil PS, Jackson DN, Gardner MO, Alexander JM, Doyle NM. Effect of intrauterine marijuana exposure on fetal growth patterns and placental vascular resistance. J Matern Fetal Neonatal Med. Oct 2021;34(20):3330-3334. doi:10.1080/14767058.2019.1683541

22. Brar BK, Brar PP, Gardner MO, Alexander JM, Doyle NM. Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses. J Matern Fetal Neonatal Med. Dec 2022;35(25):8488-8491. doi:10.1080/14767058.2021.1983538

23. Lo JO, Shaw B, Robalino S, et al. Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis. Cannabis Cannabinoid Res. Apr 2024;9(2):470-485. doi:10.1089/can.2022.0262

24. Gesterling L, Bradford H. Cannabis Use in Pregnancy: A State of the Science Review. J Midwifery Womens Health. May 2022;67(3):305-313. doi:10.1111/jmwh.13293

25. Cannabis. Drugs and Lactation Database (LactMed(R)). 2006.