Medical Marijuana

21. Lower Opioid Overdose Mortality Rates In States With Medical Cannabis Laws

"Although the mean annual opioid analgesic overdose mortality rate was lower in states with medical cannabis laws compared with states without such laws, the findings of our secondary analyses deserve further consideration. State-specific characteristics, such as trends in attitudes or health behaviors, may explain variation in medical cannabis laws and opioid analgesic overdose mortality, and we found some evidence that differences in these characteristics contributed to our findings. When including state-specific linear time trends in regression models, which are used to adjust for hard-to-measure confounders that change over time, the association between laws and opioid analgesic overdose mortality weakened. In contrast, we did not find evidence that states that passed medical cannabis laws had different overdose mortality rates in years prior to law passage, providing a temporal link between laws and changes in opioid analgesic overdose mortality. In addition, we did not find evidence that laws were associated with differences in mortality rates for unrelated conditions (heart disease and septicemia), suggesting that differences in opioid analgesic overdose mortality cannot be explained by broader changes in health. In summary, although we found a lower mean annual rate of opioid analgesic mortality in states with medical cannabis laws, a direct causal link cannot be established."

Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
jamanetwork.com...

22. Effect of CBD on Learned Fear and Potential in Treatment of Post Traumatic Stress Disorder (PTSD)

"A growing body of literature provides compelling evidence that CBD has anxiolytic effects and recent studies have established a role for CBD in regulating learned fear by dampening its expression, disrupting its reconsolidation, and facilitating its extinction. The opposing effects of CBD on fear memory reconsolidation and extinction make it particularly attractive as a potential adjunct to psychological therapy as both may lead to lasting reductions in learned fear expression. Our novel data also suggests that CBD reduces the expression of fear memory related to both discrete and contextual cues. Although we found no effect of CBD on auditory fear extinction, decreasing fear expression during extinction without interfering in its encoding is still a useful property that has clinical implications. In this respect CBD might be an improvement over other available drugs used for treating the fear-related symptoms of phobias and PTSD, which can impair extinction (e.g., benzodiazepines) or have a less favorable side effect profile (e.g., antidepressants)."

Jurkus R, Day HLL, Guimarães FS, Lee JLC, Bertoglio LJ, Stevenson CW. Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders. Frontiers in Pharmacology. 2016;7:454. doi:10.3389/fphar.2016.00454.
https://www.ncbi.nlm.nih.gov/p...
https://www.ncbi.nlm.nih.gov/p...

23. Impact of Medical Marijuana Laws on Crime Rates

"The central finding gleaned from the present study was that MML is not predictive of higher crime rates and may be related to reductions in rates of homicide and assault. Interestingly, robbery and burglary rates were unaffected by medicinal marijuana legislation, which runs counter to the claim that dispensaries and grow houses lead to an increase in victimization due to the opportunity structures linked to the amount of drugs and cash that are present. Although, this is in line with prior research suggesting that medical marijuana dispensaries may actually reduce crime in the immediate vicinity [8]."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816
http://www.plosone.org...

24. Effect of Medical Marijuana Legalization On Crime Rates

"In sum, these findings run counter to arguments suggesting the legalization of marijuana for medical purposes poses a danger to public health in terms of exposure to violent crime and property crimes. To be sure, medical marijuana laws were not found to have a crime exacerbating effect on any of the seven crime types. On the contrary, our findings indicated that MML precedes a reduction in homicide and assault. While it is important to remain cautious when interpreting these findings as evidence that MML reduces crime, these results do fall in line with recent evidence [29] and they conform to the longstanding notion that marijuana legalization may lead to a reduction in alcohol use due to individuals substituting marijuana for alcohol [see generally 29, 30]. Given the relationship between alcohol and violent crime [31], it may turn out that substituting marijuana for alcohol leads to minor reductions in violent crimes that can be detected at the state level. That said, it also remains possible that these associations are statistical artifacts (recall that only the homicide effect holds up when a Bonferroni correction is made)."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816
http://www.plosone.org...

25. Effect Of Medical Marijuana Legalization On Crime Rates

"Given that the current results failed to uncover a crime exacerbating effect attributable to MML, it is important to examine the findings with a critical eye. While we report no positive association between MML and any crime type, this does not prove MML has no effect on crime (or even that it reduces crime). It may be the case that an omitted variable, or set of variables, has confounded the associations and masked the true positive effect of MML on crime. If this were the case, such a variable would need to be something that was restricted to the states that have passed MML, it would need to have emerged in close temporal proximity to the passage of MML in all of those states (all of which had different dates of passage for the marijuana law), and it would need to be something that decreased crime to such an extent that it ‘‘masked’’ the true positive effect of MML (i.e., it must be something that has an opposite sign effect between MML [e.g., a positive correlation] and crime [e.g., a negative correlation]). Perhaps the more likely explanation of the current findings is that MML laws reflect behaviors and attitudes that have been established in the local communities. If these attitudes and behaviors reflect a more tolerant approach to one another’s personal rights, we are unlikely to expect an increase in crime and might even anticipate a slight reduction in personal crimes."

Robert G. Morris, Michael TenEyck, JC Barnes, and Tomislav V. Kovandzic, "The Effect of Medical Marijuana Laws On Crime: Evidence From State Panel Data, 1990-2006," PLoS ONE 9(3): e92816. March 2014. doi: 10.1371/journal.pone.0092816
http://www.plosone.org...

26. Harm Reduction and Alternative Delivery Methods for Cannabis Consumption

"The use of a vaporizing device may mitigate some of these symptoms. Cannabis vaporization is a technique aimed at suppressing the formation of irritating respiratory toxins by heating cannabis to a temperature where active cannabinoids are volatilized, but below the point of combustion where smoke and associated toxins form. The use of a vaporizer is associated with higher plasma THC concentrations than smoking marijuana cigarettes, little if any carbon monoxide production, and significantly fewer triggered respiratory symptoms."

American Medical Association, Council on Science and Public Health, "Report 3 of the Council on Science and Public Health: Use of Cannabis for Medicinal Purposes" (December 2009), p. 15.
http://drugwarfacts.org/cms/fi...

27. Safety of Medicinal Cannabis According to DEA Administrative Law Judge Francis Young

In 1988, the DEA's Administrative Law Judge, Francis Young, concluded: "In strict medical terms marijuana is far safer than many foods we commonly consume. For example, eating 10 raw potatoes can result in a toxic response. By comparison, it is physically impossible to eat enough marijuana to induce death. Marijuana in its natural form is one of the safest therapeutically active substances known to man. By any measure of rational analysis marijuana can be safely used within the supervised routine of medical care."

US Department of Justice, Drug Enforcement Administration, "In the Matter of Marijuana Rescheduling Petition," [Docket #86-22], (September 6, 1988), p. 57.
http://medicalmarijuana.procon.org...

28. Medicinal Cannabis and HIV-Related Neuropathic Pain

“Placebo-Controlled, Double Blind Trial of Medicinal Cannabis in Painful HIV Neuropathy”
Ronald J. Ellis, M.D., Ph.D., University of California, San Diego
(cannabis and HIV neuropathy) "The primary objective of this study also was to evaluate the efficacy of smoked cannabis when used as an analgesic in persons with HIV-associated painful neuropathy. In a double-blind, randomized, clinical trial of the short-term adjunctive treatment of neuropathic pain in HIV-associated distal sensory polyneuropathy, participants received either smoked cannabis or placebo cannabis cigarettes. A structured dose escalation-titration protocol was used to find an individualized, effective, safe, and well-tolerated dose for each subject. Participants continued on their usual analgesic medications throughout the trial, with the dose and amount of these medications being recorded daily.
"The full results of this study were published in the journal Neuropsychopharmacology (Ellis, et al., 2008 – see reference list). In brief, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among completers, pain relief was significantly greater with cannabis than placebo. The proportion of subjects achieving at least 30% pain relief was again significantly greater with cannabis (46%) compared to placebo (18%). It was concluded that smoked cannabis was generally well-tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV-associated neuropathy."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 10.
http://cdc.coop/docs/neuropath...

29. Cannabis and Cancer Pain

"• Cannabinoids, the active components of Cannabis sativa and their derivatives, act in the organism by mimicking endogenous substances, the endocannabinoids, that activate specific cannabinoid receptors. Cannabinoids exert palliative effects in patients with cancer and inhibit tumour growth in laboratory animals.
"• The best-established palliative effect of cannabinoids in cancer patients is the inhibition of chemotherapy-induced nausea and vomiting. Today, capsules of ?9-tetrahydrocannabinol (dronabinol (Marinol)) and its synthetic analogue nabilone (Cesamet) are approved for this purpose.
"• Other potential palliative effects of cannabinoids in cancer patients — supported by Phase III clinical trials — include appetite stimulation and pain inhibition. In relation to the former, dronabinol is now prescribed for anorexia associated with weight loss in patients with AIDS.
"• Cannabinoids inhibit tumour growth in laboratory animals. They do so by modulating key cell-signalling pathways, thereby inducing direct growth arrest and death of tumour cells, as well as by inhibiting tumour angiogenesis and metastasis.
"• Cannabinoids are selective antitumour compounds, as they can kill tumour cells without affecting their non-transformed counterparts. It is probable that cannabinoid receptors regulate cell-survival and cell-death pathways differently in tumour and non-tumour cells.
"• Cannabinoids have favourable drug-safety profiles and do not produce the generalized toxic effects of conventional chemotherapies. The use of cannabinoids in medicine, however, is limited by their psychoactive effects, and so cannabinoid-based therapies that are devoid of unwanted side effects are being designed.
"• Further basic and preclinical research on cannabinoid anticancer properties is required. It would be desirable that clinical trials could accompany these laboratory studies to allow us to use these compounds in the treatment of cancer."

Guzman, Manuel, "Cannabinoids: Potential Anticancer Agents." Nature Reviews: Cancer (October 2003), p. 746.
http://www.ncbi.nlm.nih.gov/pu...
http://herb.com/guzman.pdf

30. Medical Cannabis Laws and Opioid Overdose Mortality Rates

"In an analysis of death certificate data from 1999 to 2010, we found that states with medical cannabis laws had lower mean opioid analgesic overdose mortality rates compared with states without such laws. This finding persisted when excluding intentional overdose deaths (ie, suicide), suggesting that medical cannabis laws are associated with lower opioid analgesic overdose mortality among individuals using opioid analgesics for medical indications. Similarly, the association between medical cannabis laws and lower opioid analgesic overdose mortality rates persisted when including all deaths related to heroin, even if no opioid analgesic was present, indicating that lower rates of opioid analgesic overdose mortality were not offset by higher rates of heroin overdose mortality. Although the exact mechanism is unclear, our results suggest a link between medical cannabis laws and lower opioid analgesic overdose mortality."

Bacchuber, Marcus A., MD; Saloner, Brendan, PhD; Cunningham, Chinazo O., MD, MS; and Barry, Colleen L., PhD, MPP. "Medical Cannabis Laws and Opioid Analgesic Overdose Mortality in the United States, 1999-2010." JAMA Intern Med. doi:10.1001/jamainternmed.2014.4005. Published online August 25, 2014.
http://archinte.jamanetwork.co...

31. cannabis and neuropathic pain

“A Double-Blind, Placebo-Controlled Crossover Trial of the Antinociceptive Effects of Smoked Marijuana on Subjects with Neuropathic Pain“
"Barth Wilsey, M.D., University of California, Davis"
"This study’s objective was to examine the efficacy of two doses of smoked cannabis on pain in persons with neuropathic pain of different origins (e.g., physical trauma to nerve bundles, spinal cord injury, multiple sclerosis, diabetes). In a double-blind, randomized clinical trial participants received either lowdose, high-dose, or placebo cannabis cigarettes. As customary in CMCR trials, participants were allowed to continue their usual regimen of pain medications (e.g., codeine, morphine, and others).
"The full results of this study have been published in the Journal of Pain (Wilsey, et al., 2008 – see reference list). Thirty-eight patients underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis; of these, 32 completed all three smoking sessions. The study demonstrated an analgesic response to smoking cannabis with no significant difference between the low and the high dose cigarettes. The study concluded that both low and high cannabis doses were efficacious in reducing neuropathic pain of diverse causes."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 11.
http://cdc.coop/docs/neuropath...

32. The Effect of Cannabis on Neuropathic Pain in HIV-Related Peripheral Neuropathy

"The primary objective of this study was to evaluate the efficacy of smoked cannabis when used as an analgesic in persons with neuropathic pain from HIV-associated distal sensory polyneuropathy (DSPN). In a double blind, randomized, five-day clinical trial patients received either smoked cannabis or placebo cannabis cigarettes. Patients continued on any concurrent analgesic medications (e.g., gabapentin, amitriptyline, narcotics, NSAIDs) which they were prescribed prior to the trial; the dose and amount of the medications were recorded daily.
"The full results of this study appear in the journal Neurology (Abrams, et al., 2007– see reference list). In brief, 55 patients were randomized and 50 completed the entire trial. Smoked cannabis reduced daily pain by 34% compared to 17% with placebo. The study concluded that a significantly greater proportion of patients who smoked cannabis (52%) had a greater than 30% reduction in pain intensity compared to only 24% in the placebo group."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), p. 10.
http://cdc.coop/docs/neuropath...

33. Cannabis and Fibromyalgia

"We observe significant improvement of symptoms of FM [fibromyalgia] in patients using cannabis in this study although there was a variability of patterns. This information, together with evidence of clinical trials and emerging knowledge of the endocannabinoid system and the role of the stress system in the pathopysiology of FM suggest a new approach to the suffering of these patients. The present results together with previous evidence seem to confirm the beneficial effects of cannabinoids on FM symptoms."

Fiz, Jimena; Dura´n, Marta; Capella, Dolors; Carbonel, Jordi; Farre, Mag?, "Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life," PLoS Medicine (Cambridge, United Kingdom: Public Library of Science, April 2011) Vol. 6, Issue 4, p. 4.
http://www.ncbi.nlm.nih.gov/pm...

34. Cannabis and Neuropathic Pain

"In this randomized clinical trial, smoked cannabis at maximum tolerable dose (1–8% THC), significantly reduced neuropathic pain intensity in HIV-associated DSPN [distal sensory predominant polyneuropathy] compared to placebo, when added to stable concomitant analgesics. Using verbal descriptors of pain magnitude from DDS [Descriptor Differential Scale], cannabis was associated with an average reduction of pain intensity from ‘strong’ to ‘mild to moderate’. Also, cannabis was associated with a sizeable (46%) and significantly greater (vs 18% for placebo) proportion of patients who achieved what is generally considered clinically meaningful pain relief (eg X30% reduction in pain; Farrar et al, 2001). Mood disturbance, physical disability, and quality of life all improved significantly for subjects during study treatments, regardless of treatment order."

Ellis, Ronald J; Toperoff, Will; Vaida, Florin; van den Brande, Geoffrey; Gonzales, James; Gouaux, Ben; Bentley, Heather; and Atkinson, J. Hampton, "Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial," Neuropsychopharmacology (Nashville, TN : American College of Neuropsychopharmacology, 2009), Vol. 34, p. 678.
http://www.nature.com/npp/jour...

35. Pain and Medical Cannabis Use

"By providing a medical geographic patient utilization 'snapshot' of 236.4 patient-years of the use of MC [Medical Cannabis] at a regional pain clinic, this study provides further insight into the applicability of cannabinoid botanicals in the management of a broad range of refractory chronic pain conditions in adults, from myofascial pain and discogenic back pain to neuropathic pain and central pain syndromes. With physicians employing proper chart documentation of appropriate use, efficacy, and side effects at patient visits, in a manner similar to that used in opioid management of pain, there will hopefully be additional reports in the future on MC use in pain management to add to the clinical database.
"Such a literature can grow only if certain stereotypes and myths about MC use are dispelled amongst pain management specialists and their regulators. The results presented here should help to deconstruct mythologies about the kinds of patients accessing MC treatment, including their young age or their propensity to malinger or feign disease. One prominent mythology is that patients who receive treatment with MC are not 'truly sick.'45 An examination of the chart review data, which includes both subjective and objective diagnostic data substantiating patients’ chronic pain illnesses, helps to deflate this concern."

Aggarwal, Sunil K.; Carter, Gregory T.; Sullivan, Mark D.; ZumBrunnen, Craig; Morrill, Richard; and Mayer, Jonathan D., "Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State," Journal of Opiod Management, (Weston, Massachusetts: September/October 2009), Vol. 5, p. 264.
http://www.ncbi.nlm.nih.gov/pu...

36. Medicinal Cannabis and Neuropathic Pain

"We found that 25 mg herbal cannabis with 9.4% tetrahydrocannabinol, administered as a single smoked inhalation three times daily for five days, significantly reduced average pain intensity compared with a 0% tetrahydrocannabinol cannabis placebo in adult participants with chronic post-traumatic or postsurgical neuropathic pain. We found significant improvements in measures of sleep quality and anxiety. We have shown the feasibility of a single-dose delivery method for smoked cannabis, and that blinding participants to treatment allocation is possible using this method."

Ware, Mark A.; Wang, Tongtong; Shapiro, Stan; Robinson, Ann; Ducruet, Thierry; Huynh,Thao; Gamsa, Ann; Bennett, Gary J.; and Collet, Jean-Paul,"Smoked cannabis for chronic neuropathic pain: a randomized controlled trial" (Ottawa, ON: Canadian Medical Association, October 5, 2010), p. E697-E700.
http://www.cmaj.ca/cgi/reprint...

37. Analgesic Efficacy of Smoked Cannabis

"This study used an experimental model of neuropathic pain to determine whether pain induced by the injection into the skin of capsaicin, a compound which is the 'hot' ingredient in chili peppers, could be alleviated by smoked cannabis. Another aim of the study was to examine the effects of 'dose' of cannabis, and the time course of pain relief. In a randomized double-blinded placebo controlled trial, volunteers smoked low, medium, and high dose cannabis (2%, 4%, 8% THC by weight) or placebo cigarettes.
"The full results of this study were published in the journal Anesthesiology (Wallace, et al., 2007 – see reference list). Nineteen healthy volunteers were enrolled, and 15 completed all four smoking sessions. In brief, five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 minutes after cannabis exposure there was a significant decrease in capsaicin-induced pain with the medium dose (4%) and a significant increase in pain with the high dose (8%). There was no significant effect seen with low dose (2%). There was a significant inverse relationship between pain perception and plasma THC. In summary, this study suggested that there may be a 'therapeutic window' (or optimal dose) for smoked cannabis: low doses were not effective; medium doses decreased pain; and higher doses actually increased pain. These results suggest the mechanism(s) of cannabinoid analgesia are complex, in some ways like non-opioid pain relievers (e.g., aspirin, ibuprofen) and in others like opioids (e.g., morphine)."

Center for Medicinal Cannabis Research, "Report to the Legislature and Governor of the State of California presenting findings pursuant to SB847 which created the CMCR and provided state funding," University of California, (San Diego, CA: February 2010), pp. 11.
http://cdc.coop/docs/neuropath...

38. Medicinal Cannabis and Migraines

"The information reviewed above indicates that cannabis has a long established history of efficacy in migraine treatment. Clinical use of the herb and its extracts for headache has waxed and waned for 1200 years, or perhaps much longer, in a sort of cannabis interruptus. It is only contemporaneously that supportive biochemical and pharmacological evidence for the indication is demonstrable. Cannabis’ unique ability to modulate various serotonergic receptor subtypes, inhibit glutamatergic-mediated toxicities, simultaneously provide antiinflammatory activity and provide acute symptomatic and chronic preventive relief make it unique among available treatments for this disorder."

Russo, Ethan, "Hemp for Headache: An In-Depth Historical and Scientific Review of Cannabis in Migraine Treatment," Journal of Cannabis Therapeutics (September 2000) Vol. 1, pp. 73-74.
https://www.tandfonline.com/do...

39. Cannabinoids and Gastrointestinal Functions

"The role of the endocannabinoid system in the control of GI functions under physiological and pathological conditions has recently received increased interest. Within the last 5 years, more than half of all studies on the roles of the endocannabinoid system in the GI tract have been published. The current state of knowledge of the physiology and pharmacology of cannabinoids has largely increased, providing new potential tools for the treatment of several GI diseases. The symptoms of the most common GI disorders, IBS and inflammatory bowel disease, affect more than 20% of the population in Western countries and cause great discomforts [106]. Intestinal cramping, nausea, chronic diarrhoea and inflammation are all symptoms onto which the cannabinoids may be effective. Cannabis derivatives and other newly developed cannabinoids may represent promising tools for the treatment of different GI disorders because they can act at multiple sites, covering a wide spectrum of symptoms."

Massa, Federico; Storr, Martin; and Lutz, Beat, "The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract," Journal of Molecular Medicine (Berlin, Germany: August 26, 2005) Vol. 83, p. 951.
http://link.springer.com/artic...

40. Medicinal Cannabis and Nausea

"This study was designed to determine how therapeutic users of cannabis rate its effectiveness as an anti-emetic, and particularly as a treatment for nausea and vomiting of pregnancy. In general (not specific to pregnancy), the vast majority of our respondents considered cannabis to be extremely effective or effective as a therapy for nausea (93%) and vomiting (75%), and as an appetite stimulant (95%). In the context of pregnancy, cannabis was rated as extremely effective or effective by 92% of the respondents who had used it as a therapy for nausea and vomiting (morning sickness)."

Westfall, Rachel E.; Janssen, Patricia A.; Lucas, Philippe; and Capler, Rielle, "Survey of medicinal cannabis use among childbearing women: Patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness'," Contemporary Therapies in Clinical Practice (United Kingdom: November 2009) Vol. 15, Issue 4, p. 32.
http://www.ncbi.nlm.nih.gov/pu...
http://safeaccess.ca/research/...

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