Medical cannabis research
Medical cannabis research includes any medical research on using cannabis as a treatment for any medical condition. For reasons including increased popular support of cannabis use, a trend of cannabis legalization, and the perception of medical usefulness, more scientists are doing medical cannabis research. Medical cannabis is unusually broad as a treatment for many conditions, each of which has its own state of research. Similarly, various countries conduct and respond to medical cannabis research in different ways.
Cannabis use as a medical treatment has risen globally since 2008 for a variety of reasons including increasing popular support for cannabis legalization and increased incidence of chronic pain among patients. While medical cannabis use is increasing, there are major social and legal barriers which lead to cannabis research proceeding more slowly and differently from standard medical research. Reasons why cannabis is unusual as a treatment include that it is not a patented drug owned by the pharmaceutical industry, and that its legal status as a medical treatment is ambiguous even where it is legal to use, and that cannabis use carries outside the norm of a typical medical treatment. The ethics around cannabis research is in a state of rapid change.
Research by region
Research on the medical benefits of cannabis has been hindered by various federal regulations, including its Schedule I classification. To conduct research on cannabis, approval must be obtained from the Food and Drug Administration, and a license must be obtained from the Drug Enforcement Administration specific to Schedule I drugs. The FDA has 30 days to respond to proposals, while the DEA licensing can take over a year to complete. Prior to June 2015, cannabis research also required approval from the US Public Health Service. The PHS review was not performed for any other Schedule I drugs, and had no deadline imposed.
In addition to the FDA and DEA (and former PHS) requirements, the National Institute on Drug Abuse must review and approve all cannabis research. The NIDA is the only source licensed by the federal government for the cultivation and provision of cannabis, and the NIDA will not provide cannabis without first approving the research. This monopoly maintained by the DEA does not exist for other Schedule I drugs, and there is no deadline established for the NIDA review either. The quality and potency of cannabis supplied by NIDA has also been called into question by some researchers.
As a result of these requirements that have been imposed in the US, studies involving cannabis have been delayed for years in some cases, and a number of medical organizations have called for federal policy to be reformed.
A 2016 review assess the current status and prospects for development of CBD and CBD-dominant preparations for medical use in the United States, examining its neuroprotective, antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties.
In April 2018, after 5 years of research, Sanjay Gupta backed medical marijuana for conditions such as epilepsy and multiple sclerosis. He believes that medical marijuana is safer than opioid for pain management.
Research by medical condition
Cannabinoids have been shown to exhibit some anti-cancer effects in laboratory experiments, although there has been little research into their use as a cancer treatment in people. Laboratory experiments have suggested that cannabis and cannabinoids have anticarcinogenic and antitumor effects, including a potential effect on breast- and lung-cancer cells. The National Cancer Institute reports that as of November 2013[update] there have been no clinical trials on the use of cannabis to treat cancer in people, and only one small study using delta-9-THC that reported potential antitumoral activity. While cannabis may have potential for refractory cancer pain, use as an antiemetic, and as an antitumor agent, much of the evidence comes from outdated or small studies, or animal experiments.
There is no good evidence that cannabis use helps reduce the risk of getting cancer. Whether smoking cannabis increases cancer risk in general is difficult to establish since it is often smoked mixed with tobacco – a known carcinogen – and this complicates research. Cannabis use is linked to an increased risk of a type of testicular cancer.
The association of cannabis use with head and neck carcinoma may differ by tumor site, with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, confounds and misclassification of cannabis exposure.
Cannabinoids have been proposed to have the potential for lessening the effects of Alzheimer's disease. A 2012 review of the effect of cannabinoids on brain ageing found that "clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing". A 2009 Cochrane review said that the "one small randomized controlled trial [that] assessed the efficacy of cannabinoids in the treatment of dementia ... [had] ... poorly presented results and did not provide sufficient data to draw any useful conclusions".
There is emerging evidence that cannabidiol may help slow cell damage in diabetes mellitus type 1. There is a lack of meaningful evidence of the effects of medical cannabis use on people with diabetes; a 2010 review concluded that "the potential risks and benefits for diabetic patients remain unquantified at the present time".
A 2016 review in the New England Journal of Medicine said that although there was a lot of hype and anecdotes surrounding medical cannabis and epilepsy, "current data from studies in humans are extremely limited, and no conclusions can be drawn". The mechanisms by which cannabis may be effective in the treatment of epilepsy remain unclear.
Some reasons for the lack of clinical research have been the introduction of new synthetic and more stable pharmaceutical anticonvulsants, the recognition of important adverse side effects, and legal restrictions to the use of cannabis-derived medicines – although in December 2015, the DEA (United States Drug Enforcement Administration) has eased some of the regulatory requirements for conducting FDA-approved clinical trials on cannabidiol (CBD).
A 2018 study in the New England Journal of Medicine provided evidence that cannabidiol (CBD) can significantly reduce the frequency of drop seizures in patients with Lennox-Gastuat (LGS) syndrome when compared to placebo effects. The patients included in the study were aged 2-55 years old and were diagnosed with LGS, which is a rare, childhood-onset epilepsy syndrome. Some patients experienced adverse events from the use of CBD with concomitant antiepileptic drugs, including somnolence, decreased appetite, pyrexia, upper respiratory tract infections, diarrhea, and vomiting. 
In 2009, the American Glaucoma Society noted that while cannabis can help lower intraocular pressure, it recommended against its use because of "its side effects and short duration of action, coupled with a lack of evidence that its use alters the course of glaucoma". As of 2008 relatively little research had been done concerning therapeutic effects of cannabinoids on the eyes.
A 2007 review of the history of medical cannabis said cannabinoids showed potential therapeutic value in treating Tourette syndrome (TS). A 2005 review said that controlled research on treating TS with dronabinol showed the patients taking the pill had a beneficial response without serious adverse effects; a 2000 review said other studies had shown that cannabis "has no effects on tics and increases the individuals inner tension".
A 2009 Cochrane review examined the two controlled trials to date using cannabinoids of any preparation type for the treatment of tics or TS (Muller-Vahl 2002, and Muller-Vahl 2003). Both trials compared delta-9-THC; 28 patients were included in the two studies (8 individuals participated in both studies). Both studies reported a positive effect on tics, but "the improvements in tic frequency and severity were small and were only detected by some of the outcome measures". The sample size was small and a high number of individuals either dropped out of the study or were excluded. The original Muller-Vahl studies reported individuals who remained in the study; patients may drop out when adverse effects are too high or efficacy is not evident. The authors of the original studies acknowledged few significant results after Bonferroni correction.
Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS, but the 2009 review found that the two relevant studies of cannibinoids in treating tics had attrition bias, and that there was "not enough evidence to support the use of cannabinoids in treating tics and obsessive compulsive behaviour in people with Tourette's syndrome".
Anecdotal evidence and pre-clinical research has suggested that cannabis or cannabinoids may be beneficial for treating Huntington's disease or Parkinson's disease, but follow-up studies of people with these conditions have not produced good evidence of therapeutic potential. A 2001 paper argued that cannabis had properties that made it potentially applicable to the treatment of amyotrophic lateral sclerosis, and on that basis research on this topic should be permitted, despite the legal difficulties of the time.
A 2005 review and meta-analysis said that bipolar disorder was not well-controlled by existing medications and that there were "good pharmacological reasons" for thinking cannabis had therapeutic potential, making it a good candidate for further study.
Cannabinoids have been proposed for the treatment of primary anorexia nervosa, but have no measurable beneficial effect. The authors of a 2003 paper argued that cannabinoids might have useful future clinical applications in treating digestive diseases. Laboratory experiments have shown that cannabinoids found in marijuana may have analgesic and anti-inflammatory effects.
In 2014, the American Academy of Neurology reviewed all available findings levering the use of marijuana to treat brain diseases. The result was that the scientific evidence is weak that cannabis in any form serves as medicinal for curing or alleviating neurological disorders. To ease multiple sclerosis patients' stiffness, which may be accomplished by their taking cannabis extract by mouth or as a spray, there is support. The academy has published new guidelines on the use of marijuana pills and sprays in the treatment of MS.
A 2007 review said cannabidiol had shown potential to relieve convulsion, inflammation, cough, congestion and nausea, and to inhibit cancer cell growth. Preliminary studies have also shown potential over psychiatric conditions such as anxiety, depression, and psychosis. Because cannabidiol relieves the aforementioned symptoms, cannabis strains with a high amount of CBD may benefit people with multiple sclerosis or frequent anxiety attacks.
- Sagy, Iftach; Peleg-Sagy, Tal; Barski, Leonid; Zeller, Lior; Jotkowitz, Alan (March 2018). "Ethical issues in medical cannabis use". European Journal of Internal Medicine. 49: 20–22. doi:10.1016/j.ejim.2018.01.016. PMID 29482739.
- Hudak, John; Wallack, Grace (October 2015), "Ending the U.S. government's war on medical marijuana research" (PDF), Center for Effective Public Management at Brookings, The Brookings Institution
- The Obstruction Of Medical Cannabis Research In The U.S. (PDF), Americans for Safe Access, April 2009
- Zielinski, Alex (17 August 2016). "The DEA Hasn't Made Marijuana Research Any Easier". ThinkProgress. Retrieved 1 July 2017.
- The DEA: Four Decades of Impeding And Rejecting Science (PDF), Drug Policy Alliance / Multidisciplinary Associations for Psychedelic Studies, June 2014
- "Marijuana research: Overcoming the barriers". American Psychological Association. 14 September 2017. Retrieved 9 October 2017.
- Nelson, Steven (22 June 2015). "Major Pot Research Barrier Goes Up in Smoke". U.S. News & World Report. Retrieved 29 June 2017.
- Ferro, Shaunacy (13 April 2013). "Why It's So Hard For Scientists To Study Medical Marijuana". Popular Science. Retrieved 9 October 2017.
- Hellerman, Caleb (8 March 2017). "Scientists say the government's only pot farm has moldy samples — and no federal testing standards". PBS. Retrieved 9 October 2017.
- Hudak, John (11 August 2016). "The DEA's marijuana decision is more important than rescheduling". The Brookings Institution. Retrieved 9 October 2017.
- "Marijuana -- AAFP Policies". aafp.org. Retrieved 30 July 2017.
- American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use, American Academy of Pediatrics, 26 January 2015, retrieved 30 July 2017
- "Marijuana and Cancer". American Cancer Society. Retrieved 12 July 2017.
- Fasinu PS, Phillips S, ElSohly MA, Walker LA (2016). "Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents". Pharmacotherapy. 36 (7): 781–96. doi:10.1002/phar.1780. PMID 27285147.
- "Sanjay Gupta tells Jeff Sessions how marijuana can save lives from opioids". 2018-04-24.
- "CNN's Sanjay Gupta tells Jeff Sessions medical marijuana could curb opioid epidemic | TribLIVE".
- "WEED 4: Pot Vs Pills". YouTube.com.
- Bowles, DW; O'Bryant, CL; Camidge, DR; Jimeno, A (July 2012). "The intersection between cannabis and cancer in the United States". Critical Reviews in Oncology/Hematology (Review). 83 (1): 1–10. doi:10.1016/j.critrevonc.2011.09.008. PMID 22019199.
- Chakravarti, Bandana; Ravi, Janani; Ganju, Ramesh K. (17 July 2014). "Cannabinoids as therapeutic agents in cancer: current status and future implications". Oncotarget. 5 (15): 5852–5872. doi:10.18632/oncotarget.2233. ISSN 1949-2553. PMC 4171598. PMID 25115386.
- "Cannabis (marihuana, marijuana) and the cannabinoids". Health Canada. February 2013. Retrieved 2 December 2013.
- "Cannabis and Cannabinoids (PDQ®)". National Cancer Institute at the National Institutes of Health. National Cancer Institute. 2 August 2013. Retrieved 24 August 2013.
- "Cannabis and Cannabinoids: Human/Clinical Studies". National Cancer Institute. 21 November 2013. Retrieved 2 December 2013.
- Wilkie, Gianna; Sakr, Bachir; Rizack, Tina (17 March 2016). "Medical Marijuana Use in Oncology". JAMA Oncology. 2 (5): 670. doi:10.1001/jamaoncol.2016.0155. PMID 26986677.
- Arney, Kat (25 July 2012). "Cannabis, cannabinoids and cancer – the evidence so far". Cancer Research UK. Retrieved 8 December 2013.
- Gurney J, Shaw C, Stanley J, Signal V, Sarfati D (2015). "Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis". BMC Cancer (Systematic review). 15: 897. doi:10.1186/s12885-015-1905-6. PMC 4642772. PMID 26560314.
- Madras, Bertha (11 December 2015). "Update of Cannabis and its medical use" (PDF). World Health Organization. Retrieved 18 December 2016.
- Campbell VA, Gowran A (2007). "Alzheimer's disease; taking the edge off with cannabinoids?". British Journal of Pharmacology (Review). 152 (5): 655–62. doi:10.1038/sj.bjp.0707446. PMC 2190031. PMID 17828287.
- Bilkei-Gorzo A (2012). "The endocannabinoid system in normal and pathological brain ageing". Philosophical Transactions of the Royal Society of London B: Biological Sciences (Review). 367 (1607): 3326–41. doi:10.1098/rstb.2011.0388. PMC 3481530. PMID 23108550.
- Krishnan S, Cairns R, Howard R (2009). "Cannabinoids for the treatment of dementia". Cochrane Database Syst Rev (Review) (2): CD007204. doi:10.1002/14651858.CD007204.pub2. PMID 19370677.
- Di Marzo V, Piscitelli F, Mechoulam R (2011). Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol. (Review). Handbook of Experimental Pharmacology. 203. pp. 75–104. doi:10.1007/978-3-642-17214-4_4. ISBN 978-3-642-17213-7. PMID 21484568.
- Fisher M, White S, Varbiro G, et al. (2010). "The role of cannabis and cannabinoids in diabetes". The British Journal of Diabetes & Vascular Disease. 10 (6): 267–273. doi:10.1177/1474651410385860.
- Friedman D, Devinsky O (2015). "Cannabinoids in the Treatment of Epilepsy". N. Engl. J. Med. (Review). 373 (11): 1048–58. doi:10.1056/NEJMra1407304. PMID 26352816.
- Reddy, DS; Golub, V (19 January 2016). "The Pharmacological Basis of Cannabis Therapy for Epilepsy". The Journal of Pharmacology and Experimental Therapeutics. 357 (1): 45–55. doi:10.1124/jpet.115.230151. PMID 26787773.
- Pertwee RG (2012). "Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities". Philosophical Transactions of the Royal Society B: Biological Sciences (Review). 367 (1607): 3353–63. doi:10.1098/rstb.2011.0381. PMC 3481523. PMID 23108552.
- "DEA.gov / Headquarters News Releases, 12/23/15".
- Ward, Andrew (9 January 2014). "GW raises nearly $90m to develop childhood epilepsy treatment". Financial Times. Retrieved 20 January 2014.
- Devinsky, Orrin; Cross, J. Helen; Laux, Linda; Marsh, Eric; Miller, Ian; Nabbout, Rima; Scheffer, Ingrid E.; Thiele, Elizabeth A.; Wright, Stephen (25 May 2017). "Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome". New England Journal of Medicine. 376 (21): 2011–2020. doi:10.1056/NEJMoa1611618. ISSN 0028-4793. PMID 28538134.
- Devinsky, Orrin; Patel, Anup; Cross, Helen; Villanueva, Vincente; Wirrell, Elaine C.; Privitera, Michael; Greenwood, Sam M.; Roberts, Claire; Checketts, Daniel; VanLandingham, Kevan E.; Zuberi, Sameer M. (17 May 2018). "Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome". New England Journal of Medicine. 378 (20): 1888–1987. doi:10.1056/nejmoa1714631.
- Jampel, Henry (10 August 2009). "Position statement on marijuana and the treatment of glaucoma". American Glaucoma Society. Retrieved 30 November 2013.
- Yazulla S (Sep 2008). "Endocannabinoids in the retina: from marijuana to neuroprotection". Progress in Retinal and Eye Research (Review). 27 (5): 501–26. doi:10.1016/j.preteyeres.2008.07.002. PMC 2584875. PMID 18725316.
- [needs update] Kogan NM, Mechoulam R (2007). "Cannabinoids in health and disease". Dialogues Clin Neurosci. 9 (4): 413–30. PMC 3202504. PMID 18286801.
- [needs update] Singer HS (2005). "Tourette's syndrome: from behaviour to biology". Lancet Neurol (Review). 4 (3): 149–59. doi:10.1016/S1474-4422(05)01012-4. PMID 15721825.
- [needs update] Robertson MM (2000). "Tourette syndrome, associated conditions and the complexities of treatment". Brain (Review). 123 (3): 425–62. doi:10.1093/brain/123.3.425. PMID 10686169.
- Curtis A, Clarke CE, Rickards HE (2009). "Cannabinoids for Tourette's Syndrome". Cochrane Database Syst Rev (Review) (4): CD006565. doi:10.1002/14651858.CD006565.pub2. PMID 19821373.
- Iuvone T, Esposito G, De Filippis D, et al. (2009). "Cannabidiol: A promising drug for neurodegenerative disorders?". CNS Neuroscience & Therapeutics (Review). 15 (1): 65–75. doi:10.1111/j.1755-5949.2008.00065.x. PMC 6494021. PMID 19228180.
- [needs update] Carter GT, Rosen BS (2001). "Marijuana in the management of amyotrophic lateral sclerosis". The American Journal of Hospice & Palliative Care (Review). 18 (4): 264–70. doi:10.1177/104990910101800411. PMID 11467101.
- [needs update] Ashton CH, Moore PB, Gallagher P, Young AH (2005). "Cannabinoids in bipolar affective disorder: A review and discussion of their therapeutic potential". Journal of Psychopharmacology (Review, meta-analysis). 19 (3): 293–300. doi:10.1177/0269881105051541. PMID 15888515.
- Ethan B Russo (5 September 2013). Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Routledge. p. 191. ISBN 978-1-136-61493-4.
- [needs update] Di Carlo G, Izzo AA (2003). "Cannabinoids for gastrointestinal diseases: potential therapeutic applications". Expert Opinion on Investigational Drugs (Review). 12 (1): 39–49. doi:10.1517/13543718.104.22.168. PMID 12517253.
- Koppel, Barbara S., MD; et al. (29 April 2014). "Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders". Neurology. 82 (17): 1556–1563. doi:10.1212/wnl.0000000000000363. PMC 4011465. PMID 24778283.
- Naftali T, Mechulam R, Lev LB, Konikoff FM (2014). "Cannabis for inflammatory bowel disease". Dig Dis (Review). 32 (4): 468–74. doi:10.1159/000358155. PMID 24969296.
- Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO (August 2007). "Cannabidiol--recent advances". Chem. Biodivers. (Review). 4 (8): 1678–92. doi:10.1002/cbdv.200790147. PMID 17712814.
- Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS (December 2012). "Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders". Philos. Trans. R. Soc. Lond. B Biol. Sci. (Review). 367 (1607): 3364–78. doi:10.1098/rstb.2011.0389. PMC 3481531. PMID 23108553.
- Lakhan SE, Rowland M (2009). "Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review". BMC Neurology (Review). 9: 59. doi:10.1186/1471-2377-9-59. PMC 2793241. PMID 19961570.
- Lambert Center for the Study of Medicinal Cannabis & Hemp, a research institute of Thomas Jefferson University
- Center for Medical Cannabis Research, a research institute at the University of California, San Diego