51. Average Cannabis Potency in Europe and the US

"Statements in the popular media that the potency of cannabis has increased by ten times or more in recent decades are not support by the data from either the USA or Europe. As discussed in the body of this report, systematic data are not available in Europe on long-term trends and analytical and methodological issues complicate the interpretation of the information that is available. Data are stronger for medium and short-term trends where no major differences are apparent in Europe, although some modest increases are found in some countries. The greatest long-term changes in potency appear to have occurred in the USA. It should be noted here that before 1980 herbal cannabis potency in the USA was, according to the available data, very low by European standards."

King, Leslie A., European Monitoring Centre for Drugs and Drug Addiction, "EMCDDA Insights - An Overview of Cannabis Potency in Europe" (Luxembourg: Office for Official Publications of the European Communities, 2004), p. 14.

52. Estimated Lethal Dose of Cannabis

"Tetrahydrocannabinol is a very safe drug. Laboratory animals (rats, mice, dogs, monkeys) can tolerate doses of up to 1000 mg/kg (milligrams per kilogram). This would be equivalent to a 70 kg person swallowing 70 grams of the drug —about 5,000 times more than is required to produce a high. Despite the widespread illicit use of cannabis there are very few if any instances of people dying from an overdose."

Iversen, Leslie L., "The Science of Marijuana" Oxford University Press (New York, NY: 2000), p. 178.

53. Public Health Impact of Marijuana Use

"The public health burden of cannabis use is probably modest compared with that of alcohol, tobacco, and other illicit drugs. A recent Australian study96 estimated that cannabis use caused 0·2% of total disease burden in Australia—a country with one of the highest reported rates of cannabis use. Cannabis accounted for 10% of the burden attributable to all illicit drugs (including heroin, cocaine, and amphetamines). It also accounted for around 10% of the proportion of disease burden attributed to alcohol (2·3%), but only 2·5% of that attributable to tobacco (7·8%)."

Hall, Wayne and Degenhardt, Louise, "Adverse health effects of non-medical cannabis use," The Lancet (London, United Kingdom: October 17, 2009) Vol. 374, p. 1389.

54. Marijuana and Overdose Mortality

An exhaustive search of the literature finds no deaths induced by marijuana. The US Drug Abuse Warning Network (DAWN) records instances of drug mentions in medical examiners' reports, and though marijuana is mentioned, it is usually in combination with alcohol or other drugs. Marijuana alone has not been shown to cause an overdose death.

Federal Drug Abuse Warning Network (DAWN); also see Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., "Marijuana and Medicine: Assessing the Science Base," Division of Neuroscience and Behavioral Research, Institute of Medicine (Washington, DC: National Academy Press, 1999); and US Department of Justice, Drug Enforcement Administration, "In the Matter of Marijuana Rescheduling Petition" (Docket #86-22), September 6, 1988, p. 57.

55. Relative Public Health Risk of Cannabis Use

"There are health risks of cannabis use, most particularly when it is used daily over a period of years or decades. Considerable uncertainty remains about whether these effects are attributable to cannabis use alone, and about what the quantitative relationship is between frequency, quantity and duration of cannabis use and the risk of experiencing these effects.
"On existing patterns of use, cannabis poses a much less serious public health problem than is currently posed by alcohol and tobacco in Western societies."

Hall, W., Room, R. & Bondy, S., "WHO Project on Health Implications of Cannabis Use: A Comparative Appraisal of the Health and Psychological Consequences of Alcohol, Cannabis, Nicotine and Opiate Use," (Geneva, Switzerland: World Health Organization, March 1998).

56. 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.

57. Shafer Commission on Marijuana's Relative Safety

"A careful search of the literature and testimony of the nation's health officials has not revealed a single human fatality in the United States proven to have resulted solely from ingestion of marihuana. Experiments with the drug in monkeys demonstrated that the dose required for overdose death was enormous and for all practical purposes unachievable by humans smoking marihuana. This is in marked contrast to other substances in common use, most notably alcohol and barbiturate sleeping pills."

Shafer, Raymond P., et al, Marihuana: A Signal of Misunderstanding, Ch. III, (Washington DC: National Commission on Marihuana and Drug Abuse, 1972).

58. Mentions of Marijuana in Emergency Department Visits in the US, 2011

"Of the approximately 2.5 million drug misuse or abuse ED visits that occurred during 2011, a total of 1,252,500, or just over half (50.9%), involved illicit drugs (Table 4). A majority (56.3%) of illicit drug ED visits involved multiple drugs. Overall, 27.9 percent of visits involving illicit drugs also involved alcohol.
"Cocaine and marijuana were the most commonly involved drugs, with 505,224 ED visits (40.3%) and 455,668 ED visits (36.4%), respectively. Cocaine and marijuana were followed by heroin, at 258,482 ED visits, or 20.6 percent, and then by amphetamines/methamphetamine, at 159,840 visits, or 12.8 percent."

Note: According to the DAWN report, "DAWN captures drugs that are explicitly named in the medical record as being involved in the ED visit. The relationship between the ED visit and the drug use need not be causal. That is, an implicated drug may or may not have directly caused the condition generating the ED visit; the ED staff simply named it as being involved." (p. 15)

Substance Abuse and Mental Health Services Administration, Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013, p. 25 and p. 15.

59. Pulmonary Effects of Cannabis

"For physiological and pharmacological reasons,61 smoking cannabinoid herbals does not seem to have a similar health hazard profile as tobacco smoking, aside from the potential for bronchial irritation and bronchitis. Smoking cannabis was not associated with an increased risk of developing chronic obstructive pulmonary disease ..."

Aggarwal, Sunil K., "Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomized-controlled Trial Results," Clinical Journal of Pain (Philadelphia, PA: February 23, 2012), p. 4.

60. Cannabis Smoking and Pulmonary Function

"In this 20-year study of marijuana and pulmonary function, we confirmed the expected reductions in FEV1 [Forced expiratory volume in the first second of expiration] and FVC [forced vital capacity] from tobacco use. In contrast, marijuana use was associated with higher FEV1 and FVC at the low levels of exposure typical for most marijuana users. With up to 7 joint-years of lifetime exposure (eg, 1 joint/d for 7 years or 1 joint/wk for 49 years), we found no evidence that increasing exposure to marijuana adversely affects pulmonary function. This association, however, was nonlinear: at higher exposure levels, we found a leveling off or even a reversal in this association, especially for FEV1. Although our sample contained insufficient numbers of heavy users to confirm a detrimental effect of very heavy marijuana use on pulmonary function, our findings suggest this possibility."

Pletcher, Mark J., et al., "Association Between Marijuana Exposure and Pulmonary Function Over 20 Years," Journal of the American Medical Association, Jan. 11, 2012, Vol. 307, No. 2, p. 177.

61. Lung Cancer Risk from Cannabis Use

"Despite these findings, the small number of observational studies fail to demonstrate a clear association between marijuana smoking and diagnoses of lung cancer. Therefore, we must conclude that no convincing evidence exists for an association between marijuana smoking and lung cancer based on existing data. Nonetheless, certain logistic properties of marijuana smoking may increase the risk of carcinogenic exposure compared with conventional tobacco smoking, raising questions as to why observational studies have not demonstrated an association with lung cancer."

Mehra, Reena; Moore, Brent A.; Crothers, Kristina; Tetrault, Jeanette; Fiellin, David A., "The Association Between Marijuana Smoking and Lung Cancer: A Systemic Review," Archives of Internal Medicine, (Chicago, IL: American Medical Association, July 10, 2006), Vol. 166, p. 1365.

62. Cannabis and Head and Neck Squamous Cell Carcinoma

"We found that moderate marijuana use was significantly associated with reduced risk of HNSCC [head and neck squamous cell carcinoma]. This association was consistent across different measures of marijuana use (marijuana use status, duration, and frequency of use). Diminished risk of HNSCC did not differ across tumor sites, or by HPV [human papillomavirus] 16 antibody status. Further, we observed that marijuana use modified the interaction between alcohol and cigarette smoking, resulting in a decreased HNSCC risk among moderate smokers and light drinkers, and attenuated risk among the heaviest smokers and drinkers."

Liang, Caihua; McClean, Michael D., et al., "A Population-Based Case-Control Study of Marijuana Use and Head and Neck Squamous Cell Carcinoma," Cancer Research Prevention (New Milford, CT: American Association for Cancer Research, August 2009), p. 766.

63. Cancer Risk from Marijuana Use

"Nonetheless, and contrary to our expectations, we found no positive associations between marijuana use and lung or UAT cancers. Although we observed positive dose-response relations of marijuana use to oral and laryngeal cancers in the crude analyses, the trend was no longer observed when adjusting for potential confounders, especially cigarette smoking. In fact, we observed ORs <1 for all cancers except for oral cancer, and a consistent monotonic association was not apparent for any outcome. Similar findings were found when the analyses were restricted to subjects who never smoked cigarettes. The 95% confidence intervals for the adjusted ORs did not extend far above 1 (e.g., were under 2 for marijuana and lung cancer), which suggests that associations of marijuana use with the study cancers are not strong and may be below detectable limits for this type of study."

Mia Hashibe, Hal Morgenstern, Yan Cui, Donald P. Tashkin, Zuo-Feng Zhang, Wendy Cozen, Thomas M. Mack, and Sander Greenland, "Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study," Cancer Epidemiology, Biomarkers & Prevention (October 2006), p. 1833.

64. Cannabis and Lung Cancer

"Despite several lines of evidence suggesting the biological plausibility of marijuana use being carcinogenic (1), it is possible that marijuana use does not increase cancer risk, as suggested in the recent commentary by Melamede (26). Although the adjusted ORs <1 may be chance findings, they were observed for all non-reference exposure categories with all outcomes except oral cancer. Although purely speculative, it is possible that such inverse associations may reflect a protective effect of marijuana. There is recent evidence from cell culture systems and animal models that 9-tetrahydrocannabinol, the principal psychoactive ingredient in marijuana, and other cannabinoids may inhibit the growth of some tumors by modulating key signaling pathways leading to growth arrest and cell death, as well as by inhibiting tumor angiogenesis (27-29). These antitumoral associations have been observed for several types of malignancies including brain, prostate, thyroid, lung, and breast."

Mia Hashibe, Hal Morgenstern, Yan Cui, Donald P. Tashkin, Zuo-Feng Zhang, Wendy Cozen, Thomas M. Mack, and Sander Greenland, "Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study," Cancer Epidemiology, Biomarkers & Prevention (October 2006), p. 1833.

65. Cannabis and Diabetes

"In the current study, we demonstrated that chronic cannabis smokers had relative visceral adiposity and adipose tissue insulin resistance but not hepatic steatosis, glucose insulin insensitivity, impaired pancreatic b-cell function, glucose intolerance, or dyslipidemia compared with age-, sex-, ethnicity-, and BMI-matched control individuals. Our study results suggest that chronic, daily cannabis use may have differential tissue-specific effects on insulin sensitivity, but these effects appear to have minimal impact on glucose or lipid metabolism."

Muniyappa, Ranganath, MD, PhD, et al., "Metabolic Effects of Chronic Cannabis Smoking," Diabetes Care, e-published before print on March 25, 2013. DOI: 10.2337/dc12-2303. Clinical trial reg. no. NCT00428987,

66. Cannabis and Diabetes

"Our analyses of adults aged 20-59 years in the NHANES [National Health and Nutrition Examination Survey] III database showed that participants who used marijuana had lower prevalence of DM [Diabetes Mellitus] and had lower odds of DM relative to non-marijuana users. We did not find an association between the use of marijuana and other chronic diseases, such as hypertension, stroke, myocardial infarction and heart failure. This could be due to the smaller prevalence of stroke, myocardial infarction and heart failure in the examined age group.
"We noted the lowest prevalence of DM in current light marijuana users, with current heavy marijuana users and past users also having a lower prevalence of DM than non-marijuana users. The finding that past marijuana users had lower odds of prevalent DM than non-users suggests that early exposure to marijuana may affect the development of DM and a window of time of marijuana exposure earlier in life could be a factor to study. Similarly, our findings of a significant association between marijuana use and DM was only found in those aged $40 years suggest that the possibility of some protection from marijuana use may require many years before they become manifested. By contrast, it could reflect the increased prevalence of DM with age and the ability to detect an association with a lesser sample size when there is a greater cohort at risk for DM. The possible association of light marijuana use with decreased DM is similar to that of alcohol on DM and the metabolic syndrome, in which mild alcohol use was associated with lower prevalence of DM and the metabolic syndrome,14 15 and higher alcohol use associated with higher prevalence of DM and the metabolic syndrome.14 16"

Shaheen M, Norris KC, et al., "Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III." BMJ Open 2012;2:e000494. doi:10.1136/bmjopen-2011-000494.

67. Cannabis Use and Diet

Marijuana use is associated with higher daily caloric intake. In the NHANES III and CARDIA study, heavy cannabis users had ;20% higher calorie intake than nonusers (25,26). The increase in calories was from higher intake of all macronutrients. Specifically, the frequency and amount of consumption of soda, cheese, salty snacks, pork, and alcohol was higher in cannabis users. Consistent with other studies, the quality of diets consumed by cannabis users was poor (27). Furthermore, the percent of daily calories derived from carbohydrates relatively rich in simple sugars was significantly higher in marijuana smokers. These findings are consistent with human and animal studies demonstrating that cannabinoids stimulate food intake, specifically highly palatable sweet-tasting foods (28). Cannabis smokers in our study exhibited characteristics typically observed in marijuana smokers in the general population."

Muniyappa, Ranganath, MD, PhD, et al., "Metabolic Effects of Chronic Cannabis Smoking," Diabetes Care, e-published before print on March 25, 2013. DOI: 10.2337/dc12-2303. Clinical trial reg. no. NCT00428987,

68. Cannabis and Dependence

"People who develop problems with marijuana may indeed be different from those who do not, but this phenomenon has been observed with other substances of abuse. A comparison with alcohol use and dependence provides a case in point. The great majority of Americans have tried alcohol and continue to drink alcoholic beverages regularly. However, only an estimated 10 to 15 percent of alcohol drinkers develop problems, and only some of these problem drinkers seek treatment. This is also true of those who have tried cocaine or heroin (Anthony, Warner, and Kessler, 1994).
"That said, the experience of dependence on marijuana tends to be less severe than that observed with cocaine, opiates, and alcohol (Budney, 2006; Budney et al., 1998). On average, individuals with marijuana dependence meet fewer DSM dependence criteria; the withdrawal experience is not as dramatic; and the severity of the associated consequences is not as extreme. However, the apparently less severe nature of marijuana dependence does not necessarily mean that marijuana addiction is easier to overcome. Many factors besides a drug’s physiological effects—including availability, frequency and pattern of use, perception of harm, and cost—can contribute to cessation outcomes and the strength of addiction. The low cost of marijuana, the typical pattern of multiple daily use by those addicted, the less dramatic consequences, and ambivalence may increase the difficulty of quitting. Although determining the relative difficulty of quitting various substances of abuse is complex, the treatment literature reviewed here suggests that the experience of marijuana abusers rivals that of those addicted to other substances."

Budney A, Roffman R, Stephens R, Walker D. Marijuana dependence and its treatment. Addiction Science and Clinical Practice. 2007;4(1):4–16.

69. Pharmacologic Treatments for Cannabis Use Disorder (CUD)

"As research on pharmacological treatments for CUD continues, a few key findings are of note. First, cannabinoid agonists (nabilone, dronabinol in combination with lofexidine, and lofexidine alone), were the only drugs that decreased drug-taking in a human laboratory model of relapse, supporting the notion that agonist replacement and attenuation of noradrenergic activity show promise for relapse prevention. Although dronabinol alone failed to clinically reduce cannabis use, a higher dose might have been more effective. Further, that study was designed to evaluate the initiation of abstinence; dronabinol or the more bioavailable agonist nabilone, might have greater utility in the prevention of relapse [25•]. These studies also support further testing of lofexidine in combination with other drugs, and generally illustrate the utility that can be gained from combining medications.
"Second, gabapentin and NAC were the only drugs tested in placebo-controlled clinical trials that decreased cannabis use (abstinence induction). Third, the ability of a drug to reduce cannabis withdrawal symptoms is not predictive of its ability to alter drug-taking behaviors (reduce use or prevent relapse). However, all the studies that reported positive changes in drug use also reported a reduction in withdrawal during early abstinence, suggesting that this feature is an important component of an efficacious medication."

Rebecca E. Balter, Ziva D. Cooper, and Margaret Haney, "Novel Pharmacologic Approaches to Treating Cannabis Use Disorder," Current Addiction Reports, March 1, 2014, DOI 10.1007/s40429-014-0011-1.

70. Cannabis Use Disorder (CUD) Definition and Symptoms

"CUD is defined in the DSM-5 as a problematic pattern of cannabis use leading to clinically significant impairment or distress occurring within a 12-month period as manifested by cannabinoid tolerance and withdrawal; increasing amounts of cannabis use over time; inability to control consumption; craving; and recurrent cannabis use having negative implications on social, professional and educational life [3]. Withdrawal symptoms usually appear approximately 24 hours after abstinence initiation, peak within two to six days and remit within two weeks [4]. Symptoms may include irritability, anger or aggression; nervousness or anxiety; sleep difficulty (insomnia, disturbing dreams); decreased appetite or weight loss; restlessness; depressed mood; or physical discomforts (abdominal pain, shakiness/tremors, fever, chills or headache) [5, 6, 7•]. Withdrawal is diagnosed if at least three of these symptoms develop. A week after cessation of use, additional symptoms may appear such as fatigue, yawning, difficulty in concentration, and rebound periods of increased appetite or hypersomnia [3]."

Rebecca E. Balter, Ziva D. Cooper, and Margaret Haney, "Novel Pharmacologic Approaches to Treating Cannabis Use Disorder," Current Addiction Reports, March 1, 2014, DOI 10.1007/s40429-014-0011-1.

71. Smoking Behavior and Potential for Developing Dependence on Cannabis

"Differences in cannabis smoking behaviour may also represent different risks for cannabis dependence independently of total THC exposure. Similar to cigarette smokers [16,21–24], cannabis smokers typically gradually decrease the puff volume and puff duration during the course of one joint, whereas puff velocity and interpuff interval gradually increase [20]. Interestingly, in a 2-year prospective study, nicotine dependence has been shown to develop more rapidly in tobacco smokers who smoke with stable or increasing puff volume and increasing puff duration ('atypical' smoking) [16]. One interpretation of this finding is that the risk of becoming nicotine-dependent is lower in smokers who reach nicotine saturation before the cigarette is finished and decrease their pace of smoking. If this mechanism also applies to cannabis smoking, one may expect that the risk for and the severity of cannabis dependence is associated with 'atypical' cannabis smoking."

Peggy van der Pol, Nienke Liebregts, Tibor Brunt, Jan van Amsterdam, Ron de Graaf, Dirk J. Korf, Wim van den Brink & Margriet van Laar, "Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study," Addiction, March 16, 2014, doi:10.1111/add.12508.

72. Medical Cannabis Patients and Other Drug Use

"Analysis of the demographic and social characteristics of a large sample of applicants seeking approval to use marijuana medically in California supports an interpretation of long term non problematic use by many who had first tried it as adolescents, and then either continued to use it or later resumed its use as adults. In general, they have used it at modest levels and in consistent patterns which anecdotally-often assisted their educational achievement, employment performance, and establishment of a more stable life-style. These data suggest that rather than acting as a gateway to other drugs, (which many had also tried), cannabis has been exerting a beneficial influence on most."

Thomas J O'Connell and Ché B Bou-Matar, "Long term marijuana users seeking medical cannabis in California (2001–2007): demographics, social characteristics, patterns of cannabis and other drug use of 4117 applicants," Harm Reduction Journal, (November 2007).

73. High-Potency Cannabis and Potential For Developing Dependence

"This study among 98 experienced cannabis smokers is the first naturalistic study to examine whether users of cannabis with high THC concentration titrate the psychoactive effects by using lower doses and/or by reduced inhalation, and whether cannabis smoking behaviour (topography) predicts cannabis dependence severity independently of total THC exposure.
"In contrast to our hypothesis, there was a positive association between cannabis THC concentration and cannabis dose, indicating that users of stronger cannabis generally used larger amounts of cannabis to prepare their regular joint. However, in line with our hypothesis, the negative association between THC concentration of joints and total inhaled smoke volume indicates that users of stronger joints inhaled smaller smoke volumes, thus resulting in partial titration of the total THC exposure. Overall, as exemplified by the comparison of the average user with the user with the maximum THC concentration, users of high-potency cannabis will generally be exposed to higher total doses of THC (at least in this sample). This is in line with Cappell et al.’s observations through a one-way mirror experiment in 1973 where users only partly adapted their intake [14]. Indeed, increased THC concentrations of cannabis have recently been linked to increased internal THC exposure assessed in blood [28]."

Peggy van der Pol, Nienke Liebregts, Tibor Brunt, Jan van Amsterdam, Ron de Graaf, Dirk J. Korf, Wim van den Brink & Margriet van Laar, "Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study," Addiction, March 16, 2014, doi:10.1111/add.12508.

74. High-Potency Cannabis and Titration of Dosage Among Experienced Users

"Although experienced young adult cannabis users with a preference for stronger joints titrated their THC exposure to some extent by inhaling less smoke, in general more potent cannabis was used in higher dosages leading to a higher THC exposure compared to users preferring lower potency cannabis. None the less, in our population of frequent cannabis users, total THC exposure was only a weak predictor of dependence severity, and did not remain significant after adjustment for baseline dependence severity. However, cannabis smoking behaviours predicted cannabis dependence severity independently of baseline THC exposure and baseline cannabis dependence severity. As the amount of explained variance was low, due possibly to the multifactorial aetiology of dependence, future studies should include other predictors, such as genetic variations, early traumatic experiences and — most importantly — time-dependent variables representing the dynamic nature of personal and dependence development. Meanwhile, smoking variables, such as smoking topography and completely finishing high-dose/high-potent joints in one smoking session, may be helpful to identify people at risk of escalating cannabis dependence severity."

Peggy van der Pol, Nienke Liebregts, Tibor Brunt, Jan van Amsterdam, Ron de Graaf, Dirk J. Korf, Wim van den Brink & Margriet van Laar, "Cross-sectional and prospective relation of cannabis potency, dosing and smoking behaviour with cannabis dependence: an ecological study," Addiction, March 16, 2014, doi:10.1111/add.12508.

75. Cannabinoid Withdrawal

"The withdrawal syndrome associated with dronabinol, the API [Active Pharmaceutical Ingredient] in Marinol®, produces symptoms in humans such as restlessness, irritability, mild agitation, anxiety, anger, insomnia, sleep EEG disturbances, nausea, decreased appetite, and decreased weight. Since a withdrawal syndrome is indicative of physical dependence, it is reasonable to conclude that generic dronabinol products (both naturally-derived [from the cannabis plant] or synthetically produced, and in hard or soft gelatin capsules) in sesame oil, will also produce physical dependence similar to those produced by Marinol®."

Federal Register, "Listing of Approved Drug Products Containing Dronabinol in Schedule III," Vol. 75, No. 210, Monday, November 1, 2010, pp. 67054 to 67059.
"MARINOL® (dronabinol) Capsules," (Abbott Laboratories: Abbott Park, IL, July 2006), pp. 11.