'Cannabis Load': Measuring Intensity of Cannabis Use and its

Association to Cannabis Use Disorder

Daniel Feingold PhD1, Ofir Livne MD2, Jürgen Rehm, PhD3,4,5 & Shaul Lev-Ran, MD2,3,6

1
Department of Psychology, Ariel University, Ariel, Israel.

2
Lev Hasharon Medical Center, Netanya, Israel.

3
Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto,

Ontario, Canada

4
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

5
Technische Universität Dresden, Klinische Psychologie & Psychotherapie, Dresden, Germany

6
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Running head: 'Cannabis Load' and Cannabis Use Disorder

Corresponding author:

Daniel Feingold, PhD

Department of Psychology, Ariel University, Ariel, Israel

Telephone: 972-(0)98981111 Fax: 972-(0)777031982 Email:

d.y.feingold@gmail.com
Abstract

Background and Objectives: Frequency and quantity of cannabis use are considered 'gold

standard' in screening for pathological cannabis use. However, using a single component for

assessing intensity of cannabis use has been criticized and considered insufficient. In this study,

we introduce a novel measure of cannabis use intensity–'cannabis load'–an aggregate of

frequency and quantity measures of cannabis use.

Methods: Participants were lifetime cannabis users (N=11,272) from the 2012-2013 National

Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). Cannabis load was

constructed by multiplying values of frequency (number of days per week) and quantity (mean

number of joints smoked per day) of cannabis use, indicating the number of joints smoked per

week at the time when using cannabis the most. Univariable and multivariable discrete-time

survival analyses identified predictors of transition from cannabis use to DSM-5 Cannabis Use

Disorder (CUD), based on cannabis load values.

Results: Cannabis users with cannabis load values of approximately 7, 21, 56 and 80 joints/week

had a 24%, 51%, 86% and 95% probability of transitioning to CUD, respectively. When using

cannabis load as the unit of analysis, male cannabis users had a lower risk (adjusted Hazards

Ratio (aHR)=0.84, 95% CI=0.73-0.96) of transitioning to CUD compared to female users.

Significant associations with transition to CUD were also shown for: race, educational level,

personality disorders, TUD, and DUD.

Discussion and Conclusions: Cannabis load may serve as a promising measure for exploring

the probability of transition to CUD.

Scientific Significance: Contribution towards standardization of cannabis exposure intensity.

Keywords: Marijuana; Cannabis load; Cannabis Use Disorder; DSM-5; Survival analysis

Narrative: 4230

Number of Tables: 2

Number of Figures: 2

Number of References: 69
Introduction
Cannabis is the most widely used drug in the world (1). With a 16% increase in its global

prevalence reported between 2006-2016, it is now estimated that more than 190 million

individuals use cannabis each year worldwide (2). Cannabis use has been associated with

increased risk for several adverse consequences, including motor-vehicle collision (3), lower

birth weight (related to cannabis use during pregnancy (4)) and increased risk of psychotic

disorders among susceptible individuals (5). In addition, among lifetime cannabis users,

approximately 34% may meet the criteria for a diagnosis of DSM-IV Cannabis Use Disorder

(CUD) (i.e. cannabis abuse or dependence), half of which within 3 years following first use (6).

A growing number of studies (5, 7, 8) have shown that the odds for adverse consequences among

cannabis users increase with more intense use of cannabis; nevertheless, a clear definition for

intensity of cannabis use and its predictive value of various detrimental outcomes associated with

cannabis use is missing (9).

To-date, studies addressing intensity indices of cannabis use and their associations with

cannabis CUD have focused on either frequency or quantity of cannabis use for measuring

intensity of cannabis use. Frequency of cannabis use has commonly been regarded as the number

of days an individual uses cannabis within a certain period of time (9). It has been suggested that

rates of transition from cannabis use to CUD are higher with increased frequency of use, with

approximately 50% of daily cannabis users developing CUD throughout their lifetime (7).

Quantity measures of cannabis use are commonly defined as the number of joints smoked or

grams of cannabis consumed per day; results from past studies indicate that consumption of a

higher quantity of cannabis is associated with an increased risk for CUD (8, 10).

Assessing intensity levels of cannabis use by using a single cannabis use component has

been widely criticized and considered to be an insufficient, and thus an unreliable, measure of
intensity of cannabis use (9). Relying on a single cannabis consumption measure (i.e., frequency

or quantity) as a predictive clinical marker has shown insufficient predictive validity (11) and has

been reported to account for only a small portion of the variance in cannabis-related negative

consequences (12). This may be due to the fact that using a single cannabis consumption

measure poorly distinguishes between various common patterns of cannabis use; for example,

daily cannabis use unanimously refers to individuals who use one joint per day and those using

ten joints. Respectively, smoking one joint per day in days when using cannabis does not

distinguish those smoking one joint once a week and those smoking one joint each day. It has

been suggested that one 'joint-year' (being exposed to one cannabis joint or equivalent per day in

a one- year period) is associated with a 0.3% increase in prevalence of chronic obstructive

pulmonary disease (COPD (13)). However, there is currently lack in data concerning the extent

to which an integrative measure of cannabis use intensity may be associated with transition to

CUD (9, 14).

In addition to intensity of cannabis use, several specific factors, such as race, gender and

age at onset of cannabis use, have been shown to affect the odds of transition from cannabis use

to CUD (15-18). Furthermore, it has been suggested that the probability of transition to CUD

should be explored within a developmental framework, (19-21), due to the fact that it commonly

occurs during late adolescence or early adulthood (22). Accordingly, some evidence suggests

that childhood abuse, childhood maltreatment or parental loss may increase the odds of transition

to CUD (23-25). However, the extent to which these above-mentioned factors are associated

with intensity of cannabis use and its role in the transition to CUD cannabis use disorder is yet

unknown.
 In this study, we introduce a novel measure of cannabis use intensity – 'cannabis load' –

an aggregate of frequency and quantity measures of cannabis use. Drawing on a large-scale

nationally representative sample of U.S. adults, we explored the rates of transition from cannabis

use to a DSM-5 diagnosis of CUD, based on cannabis load values in the general population and

across several categories of sociodemographic and clinical factors.

Materials and Methods

NESARC-III Sample

The NESARC-III target population was civilians ≥18 years in households and selected

group quarters (26, 27). Respondents were selected through multistage probability sampling,

including primary sampling units (counties/groups of contiguous counties); secondary sampling

units (SSU; groups of Census-defined blocks); and tertiary sampling units (households within

SSUs) from which respondents were selected, with Blacks, Asians, and Hispanics oversampled.

Data were adjusted for nonresponse and weighted to represent the U.S. population based on the

2012 American Community Survey (28). These weighting adjustments compensated adequately

for nonresponse. Face-to-face interviews in respondents’ homes were conducted with 36,309

participants. The overall response rate was 60.1%, comparable to other current U.S. national

surveys (29, 30). NESARC-III methodology is described further elsewhere (27). Institutional

review boards at the National Institutes of Health and Westat approved the study protocol.

Assessments

The NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-5

(AUDADIS-5) was the diagnostic interview. AUDADIS-5 measures drug and alcohol use (e.g.,
onset, frequency), DSM-5 drug, alcohol and nicotine use disorders, and selected psychiatric

disorders in the last 12 months and prior to the last 12 months (31).

Cannabis Use

In accordance with National Institute on Alcohol abuse and Alcoholism (NIAAA)

epidemiological reports, as well as past NESARC-III publications, in the current study twelve-

month and prior to 12-month cannabis use items were computed to form an aggregated variable

of lifetime cannabis use (32). In accordance with the DSM-5 Substance Use Disorder (SUD)

diagnostic criteria, CUD diagnosis required 2 of 11 criteria (33) within any period throughout

participants’ lives. Test-retest reliability of lifetime cannabis use was substantial (kappa=0.78,

0.77) in a general population sample (34). Test-retest reliabilities of DSM-5 cannabis use

disorders (kappa=0.41, 0.41) and their dimensional criteria scales (intraclass correlation

coefficients [ICC]=0.70, 0.71) were fair to substantial in a general population sample (35).

Intensity of cannabis use

Intensity of cannabis use was measured using 'cannabis load', a novel construct

integrating frequency and quantity of cannabis use. Frequency of cannabis use was assessed

using a question pertaining to the time of heaviest marijuana use: “at the time you were using

marijuana the most, how often did you use marijuana?”. Participants replied with one of the

following answers: 1) every day; 2) nearly every day; 3) three to four times a week; 4) one to

two times a week; 5) two to three times a month; 6) once a month; 7) seven to eleven times a

year; 8) three to six times a year; 9) two times a year; 10) once a year. This variable was recoded

to indicate the number of days (i.e., times) per week in which respondents used cannabis during

that period; for instance, a participant reporting to have used marijuana between 2-3 times a

month was considered to have consumed marijuana 2.5 times a month; this average value was
multiplied by 12 (months per year), divided by 365 (days per year) and multiplied by 7 (days per

week), indicating the number of days marijuana was consumed per week (0.575). A participant

reporting to have used marijuana 3 to 6 times in the last year received a value of 0.086 (4.5

divided by 365, multiplied by 7). The quantity of cannabis use was assessed using the following

question: “At the time you were using marijuana the most, about how many joints did you

usually smoke in a single day?”; replies were provided by participants in numerical values

(continuous). Addressing intensity of cannabis use during the time of heaviest use throughout

one’s lifetime has been previously reported to predict adverse consequences of cannabis use

(36); furthermore this measure has been incorporated in previous NESARC studies that

examined negative outcomes of cannabis use (37). In addition, utilizing queries assessing 12-

month cannabis use patterns could substantially limit the current study’s sample size, therefore

we used questions pertaining to lifetime cannabis use patterns.

Multiplying values for these variables (i.e., recoded frequency variable and quantity

variable) produced an aggregate variable, cannabis load, indicating the number of joints

participants smoked per week at the time of heaviest cannabis use. In order to compare the

predictive accuracy of cannabis load to frequency and quantity of cannabis use variables,

goodness of fit tests were performed with lifetime CUD as the outcome, and frequency and

quantity of cannabis use, as well as cannabis load as individual predictors; likelihood-ratio test

showed that overall all models were significant. Concordance index values were shown to be

strong and comparable for two analyses – a forward stepwise logistic regression, including

frequency and quantity of cannabis use; a regression including cannabis load as a predictor

(0.858, 0.859, respectively). Further goodness of fit tests demonstrated a lower AIC for cannabis
load as a predictor of CUD compared to frequency and quantity of cannabis use (1307.075,

11248.607, 10927.358, respectively).

Sociodemographic Covariates

These included sex, race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Hispanics,

Asians or Pacific Islanders, and Native Americans), age, marital status, education, 12-month

household income, urbanicity, and region.

Psychiatric and Substance Use Disorder Covariates

Psychiatric disorders included: any mood disorder (major depressive disorder, dysthymia,

bipolar 1 and bipolar 2); any anxiety disorder (generalized anxiety disorder, social phobia,

agoraphobia, specific phobias, and panic disorder); any personality disorder (borderline,

schizotypal, and antisocial). Test-retest reliability was fair to moderate for depressive (k=0.39-

0,40) and anxiety disorders (k=0.43-0.51), with generally good to excellent reliability for

corresponding dimensional measures (intraclass correlation coefficients, 0.59-0.79) (31).

Lifetime SUDs included Alcohol Use Disorder (AUD); Tobacco Use Disorder (TUD); and other

Drug Use Disorders (DUDs), the latter coded positive for the following substances: cocaine,

hallucinogens, opioids, sedatives, inhalants/solvents, heroin, club drugs, stimulants, and ‘other

drugs’.

Childhood Adversity Covariates

AUDADIS-5 questioned participants about childhood adversities (CA) experienced prior to the

age of 18. These included: emotional and physical abuse, exposure to domestic violence, neglect,

endangerment, sexual abuse, and parental dysfunction. Both emotional and physical abuse were

assessed using questions from the Conflict Tactics Scale (38). Emotional abuse was measured by

three items that assessed the frequency that caretakers insulted or swore at, said hurtful things,
and threatened respondents with violence. Physical abuse was measured by two items that

examined the frequency with which caregivers pushed, hit, or bruised the respondent.

Domestic violence exposure was assessed through four questions examining the

frequency with which violent behaviour was directed at the respondent’s female caregiver.

Neglect was assessed using items from the Childhood Trauma Questionnaire (39). Endangerment

was assessed using a single query questioning participant whether they were made to do chores

that were dangerous for someone their age. Sexual abuse was assessed using four previously

validated questions about unwanted sexual experiences that involved an adult or that occurred

when the respondent was too young to know what was happening. Respondents reported the

frequency of exposure childhood adversities on a scale from 1 (never) to 5 (very often), except

for sexual assault before the age of 18, which was a dichotomous variable (‘yes/no’ response).

Three types of CA related to parental dysfunction due to serious mental illness, incarceration, or

alcohol and drug abuse were examined. In accordance with a past approach to coding CA

variables (40) and as incorporated previously in NESARC data by Myers et al. (2014) – CA

categories’ scores were summed, creating a categorical variable that assessed the number of

childhood adverse events respondents were exposed to (0; 1-2; 3 or above) (41).

Statistical Analysis

Weighted frequencies of cannabis use covariates were calculated to characterize the

analytic sample of lifetime cannabis users (N=11,272) and chi square analyses were employed in

comparison to non-users.

In order to examine the association between known CUD covariates and the hazards

of transitioning from cannabis use to CUD, we performed a univariable discrete-time survival

analysis; cannabis load values were used as the unit of analysis (42). This survival analysis was
implemented in a sub-sample of cannabis users reporting their age at heaviest use to occur prior

to their age at first occurrence of CUD (N=1,576). Covariates that were examined as possible

predictors of transitioning to CUD included sociodemographics and clinical correlates of CUD

(psychiatric disorders), as well as childhood adverse events. Further multivariable discrete-time

survival analyses were performed examining the association between these predictors and the

hazards of transitioning to CUD, while controlling for all other covariates in three controlled

models: the first model controlled for sociodemographic characteristics; the second model

controlled for sociodemographic characteristics and personality disorders; the third model

controlled for sociodemographic characteristics and other SUDs (TUD, DUD). These analyses

were implemented in SUDAAN (version 11.0.3) (43) using PROC SURVIVAL to accommodate

for the complex survey design. Results were regarded as meaningful when an association was

found to be significant (p<0.05, 2-tailed tests) in unadjusted models and remained significant in

all adjusted models (models 2,3,4).

Using the actuarial method (44), we assessed the cumulative probability of transitioning

from cannabis use to CUD according to cannabis load values with a maximum value set at 140

(Figures 1,2). Although NESARC-III is a cross-sectional survey, considering that AUDADIS-5

collected data on participants’ age at the period of heaviest cannabis use, and on their age at

onset of first episode of a DSM-5 CUD, we were able to more accurately estimate rates of

transition of cannabis use to CUD. An “event” (i.e., CUD) is commonly defined in a lifetime

context in survival analyses; considering this, and since utilizing queries assessing 12-month

cannabis use patterns could substantially limit the current study’s sample size, we used questions

pertaining to lifetime cannabis use and CUD. Based on results from univariable and

multivariable discrete-time survival analyses, using the log-rank test, we examined whether
survival curves differed statistically between males and females. These analyses were calculated

for the entire NESARC-III sample of cannabis users (N=11,272) and implemented in an analytic

sample of cannabis users reporting their age at heaviest use to occur before their age at first

CUD (N=1,576), using PROC LIFETEST (SAS version 9.4), as previously performed on

NESARC data (15).

Results

Sample Characteristics

Lifetime cannabis users (N=11,272) represented 32.2% (SE=0.54) of the NESARC-III sample.

These were primarily male (57%); white (73%); college educated (65%); married or living with

someone as if married (54%); and with a household income of above 70,000$ (33%) (Table 1).

The mean age at onset of cannabis use among these individuals was 17.6 years (SE=0.06). The

majority of lifetime cannabis users were aged 45-64 (39%), while lifetime users aged 18-29, 30-

44, and 65 or older represented 27%, 29%, and 6%, respectively.

1,567 lifetime cannabis users reported a younger age at their heaviest period of cannabis use than

their age at first occurrence of CUD (after eliminating missing variables). Mean age at period of

heaviest cannabis use was 18.7 years and mean age at first occurrence of CUD was 19.4 years.

univariable / multivariable analyses

Sociodemographics

Gender and educational level were shown to be significant predictors of transition from

cannabis use to CUD, when using cannabis load as the unit of analysis in univariable and

multivariable models (Table 2). Male cannabis users had a lower risk (adjusted hazards ratio,

model 1 [aHR]= 0.84, 95% CI 0.73-0.96) of transitioning to CUD than female cannabis users. In
other words, for all cannabis load values (number of joints smoked per week), women had a

higher probability of transitioning to CUD, compared to men with similar cannabis load values.

Psychiatric and substance use disorders

Personality disorders, TUD, and DUD were significantly associated with the transition

from cannabis use to CUD, when using cannabis load as the unit of analysis in univariable and

all multivariable models (aHR=0.77, 95% CI 0.68-0.86; aHR=0.79, 95% CI 0.68-0.92;

aHR=0.65, 95% CI 0.57-0.74 ). .

Childhood adversities

The number of childhood adverse events was not shown to be a significant predictor of

CUD, when using cannabis load as the unit of analysis.

Probability of transition to CUD (survival analyses)

The cumulative probability of transitioning from cannabis use to CUD among users with

a cannabis load of 7 (joints/week) was 24%. Cannabis users with a cannabis load value of

approximately 14 (joints/week), 21 (joints/week), 35 (joints/week), 56 (joints/week), 80

(joints/week) and 140 (joints/week) had a ~40%, ~51%, 71%, 86%, 95%, and 97% probability of

transitioning to CUD, respectively (Figure 1). The plateau area in figure 1 shows that there were

no substantial differences in the probability of transitioning to CUD for cannabis load values

between the range of 70-140 (joints/week). In order to quantify the association between cannabis

load and CUD, we performed a logistic regression analysis, controlling for sociodemographic

and clinical covariates shown to be associated with CUD (sex, age, race, education, 12-month

family income, marital status, any lifetime mood or anxiety disorders, personality disorders,

lifetime SUD, duration from cannabis onset to CUD), with cannabis load as a predictor and
lifetime CUD as an outcome; a one unit increase in cannabis load value was shown to lead to a

1.12 fold increase in the odds of lifetime CUD (95% CI 1.02-1.04).

Differences in levels of predictors (log-rank tests)

Probability estimates indicated that female cannabis users were more likely to transition to CUD

for all cannabis load values (p<0.005; Figure 2). A 50% probability of transitioning to CUD was

associated with cannabis load values of 15 and 21 for female and male users, respectively.

Female cannabis users with a cannabis load value of approximately 7, 14, 35, 56, 80, and 140

had a 28%, 43%, 74%, 88%, 95%, and 98% probability of transitioning to CUD, respectively

(Figure 2). Male cannabis users with a cannabis load value of approximately 7, 14, 35, 56, 80,

and 140 had a had a 22%, 37%, 69%, 85%, 94% and 96% probability of transitioning to CUD,

respectively (Figure 2).

Discussion

In this study, we sought to explore the probability of transition from cannabis use to a

DSM-5 diagnosis of CUD, according to values of a novel cannabis use intensity construct –

cannabis load – a potential measure of intensity of cannabis use. Results indicate that among

participants who reported using at least 21 joints per week during the time when using cannabis

the most, 50% met the diagnostic criteria for CUD. In addition, findings indicated that women

had a higher probability of transitioning to CUD compared to men for all cannabis load values.

Based on our analysis, more than half of individuals who smoked approximately 21 joints

per week, equivalent to 3 joints per day or above in the time when using cannabis the most, met

the diagnostic criteria for a lifetime diagnosis of CUD. In previous studies, frequency and
quantity of cannabis use have been shown to independently account for cannabis-related

problems (45), indicating that such problems more commonly occur among individuals using

cannabis 12 days or more per month and those smoking 3.5-8 joints per day of cannabis use (46).

According to data from NESARC wave 1 (2001-2002), cannabis users who qualified for a

diagnosis of DSM-IV cannabis abuse used cannabis, on average, 153.2 days in the past year,

smoking, on average, 2.4 joints per day of cannabis use; this is roughly equivalent to 30.6 joints

per week. Cannabis users who qualified for a diagnosis of cannabis dependence used cannabis

232.3 days annually, smoking 4.03 joints per day; roughly equivalent to 48.4 joints per week

(47).

As previously suggested, there may be a dose-response effect in the association between

intensity of cannabis use and the risk of developing a CUD (48). According to our findings,

within the lower range of cannabis load values, an increase of seven joints per week (i.e., one

joint per day) is associated with an approximate 11% lifetime probability of transition to CUD.

Notably, this effect seems to reach a plateau around a cannabis load value ranging between 70-

80, with a cumulative probability of approximately 90% of transition to CUD. This reported

plateau at 70-80 joints per week may be attributed to a celling effect occurring when individuals

are under the influence of cannabis during most part of their waking hours, while smoking 140

joints per week may result in cannabis intoxication and related health problems (49), which are

intrinsic to CUD – yet this should be further explored.

Notably in our study, women exhibited higher odds for transition to CUD for all values of

cannabis load, suggesting that for any weekly quantity of cannabis use, women are at higher risk

for transition to CUD. Generally, women are less prone to use or misuse drugs and alcohol (50),

yet an accelerated progression across time from first use to SUD among women has been
reported in studies focusing on alcohol dependence, opioid dependence, CUDs and pathological

gambling (51-53). In addition, research has indicated that adverse neurological effects of

substance use, such as brain atrophy due to heavy alcohol consumption, may occur more rapidly

among women compared to men (54). Preclinical research has indicated that this pattern may be

attributed to hormonal and chromosomal differences associated with gender-specific

development (50). According to our findings, it is possible that among female cannabis users this

effect may in part be attributed to higher susceptibility to CUD caused by greater sensitivity to

cannabis use intensity.

In our study, individuals who qualified for a lifetime diagnosis of personality disorders,

TUD or DUD exhibited lower risk for transition to CUD when incorporating cannabis load as the

unit of analysis. Among cannabis users, these disorders have been repeatedly reported to increase

the odds for transition to cannabis dependence or abuse (6, 15), presumably in part due to brain-

level dopaminergic dysfunction present among individuals suffering from a co-occurring

psychiatric disorder (55). It may well be that among cannabis users, the presence of a co-

occurring personality disorder, TUD or DUD may in itself be a dominant predictor for transition

to CUD, diminishing the effect of cumulative exposure to cannabis load as a risk factor among

these individuals Notably, despite evidence that childhood adversities are associated with SUDs,

including increased odds for transition to CUD (56, 57), our results do not suggest that this

association can be attributed to changes in cannabis load.

Addressing our results, several limitations should be considered. First, despite the fact

that retrospective self-reported accounts of cannabis use are generally reliable (58), cannabis

load was assessed based on frequency and quantity indices at the time when participants were

using cannabis the most, therefore the duration of this period is unknown and does not
necessarily imply a consecutive pattern of cannabis use. Nevertheless, addressing the time when

using cannabis the most has been previously reported to be highly predictive of adverse

consequences of cannabis use (36). Furthermore, due to the nature of the NESARC-III sample, a

reversed association could not be ruled out, i.e. that for some participants transition to CUD

preceded the time in which they used cannabis the most. It has suggested that persistent cannabis

dependence may lead to an increase in frequency of cannabis use over time (59), therefore it may

well be that for some cannabis users transition to CUD may in fact increase cannabis load and

not vice-versa. Second, in the past two decades there has been a change in the social perception

around the legitimacy of cannabis use, alongside recent changes in its legal status in several U.S.

states; however, cannabis use may be still under-reported in the NESARC-III sample due to

matters of privacy and anonymity in the NESARC-III sample, as well as response bias, which

may stem from social desirability, i.e. respondents' tendency to align with social norms (60).

Therefore, cannabis load values associated with transition to CUD may be in fact somewhat

higher from those reported in this study and should be taken under consideration in future

research (61). Furthermore, NESARC-III does not include data regarding the concentrations,

potency or mode of administration of different cannabinoids used, all which may affect the risk

for negative outcomes, (8). Future studies should attempt to incorporate these factors in the

cannabis load construct, in order to create a multidimensional intensity construct of cannabis use

that could assist researchers in identifying more accurately predictors of transition from cannabis

use to CUD.

Despite these limitations, cannabis load may serve as a promising measure when

exploring adverse consequences of cannabis use. Further prospective studies should pursue the

construction of a more comprehensive and predictive cannabis use intensity measure (compared
to its components’ predictive value) that will include not only elaborate frequency and quantity

measures, but also information about other cannabis use components, such as: mode of use,

potency and strains of cannabinoids used. Future research should evaluate its unique predictive

value in assessing the association between cannabis use and psychosis (62), mood and anxiety

disorders (63, 64) and impaired psycho-social functioning (65). In addition, cannabis load may

be a useful clinical tool, which will allow clinicians to screen for high-risk patterns of cannabis

use which may be associated with future onset of CUD, resembling the intuitive use of 'pack

years' or 'standard drinks' in screening for pathological alcohol consumption and tobacco use (66,

67). With a constant increase in its global prevalence in recent years, efforts are made to develop

effective tools for assessing CUD in the general population. Frequency of cannabis use is

currently considered a 'gold standard' in screening for pathological cannabis use (68), yet

combining various measures of cannabis use has previously shown to strengthen the validity of

predicting pathological cannabis use in clinical samples (69). Therefore, cannabis load may be

useful construct in further understanding potential negative health consequences of cannabis use.

Acknowledgments: None.

Declarations of Interest: The authors report no conflicts of interest.

References

1. WHO. The health and social effects of nonmedical cannabis use. Geneva, CH: WHO, 2016.
2. United Nations Office on Drugs and Crime. World Drug Report, 2018. New York: 2018.
3. Rogeberg O, Elvik R. The effects of cannabis intoxication on motor vehicle collision revisited and
revised. Addiction. 2016;111:1348-1359.
4. Gunn J, Rosales CB, Center K, Nuñez A, Gibson S, Christ C, et al. Prenatal exposure to cannabis
and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open.
2016;6:e009986.
5. Marconi A, Di Forti M, Lewis CM, Murray RM, Vassos E. Meta-analysis of the association
between the level of cannabis use and risk of psychosis. Schizophr Bull. 2016;42:1262-1269.
6. Marel C, Sunderland M, Mills KL, Slade T, Teesson M, Chapman C. Conditional probabilities of
substance use disorders and associated risk factors: Progression from first use to use disorder on
alcohol, cannabis, stimulants, sedatives and opioids. Drug Alcohol Depend. 2019;194:136-142.
7. Looby A, Earleywine M. Negative consequences associated with dependence in daily cannabis
users. Subst Abuse Treat Prev Policy. 2007;2:3.
8. van der Pol P, Liebregts N, de Graaf R, Korf DJ, van den Brink W, van Laar M. Predicting the
transition from frequent cannabis use to cannabis dependence: a three-year prospective study. Drug
Alcohol Depend. 2013;133:352-359.
9. Temple EC, Brown RF, Hine DW. The ‘grass ceiling’: limitations in the literature hinder our
understanding of cannabis use and its consequences. Addiction. 2011;106:238-244.
10. Chen K, Kandel DB, Davies M. Relationships between frequency and quantity of marijuana use
and last year proxy dependence among adolescents and adults in the United States. Drug Alcohol
Depend. 1997;46:53-67.
11. Buu A, Hu Y-H, Pampati S, Arterberry BJ, Lin H-C. Predictive validity of cannabis consumption
measures: Results from a national longitudinal study. Addict Behav. 2017;73:36-40.
12. Pearson M. A meta-analytic investigation of the associations between cannabis use and
cannabis-related negative consequences. Psychology of addictive behaviors: journal of the Society of
Psychologists in Addictive Behaviors. 2019.
13. Macleod J, Robertson R, Copeland L, McKenzie J, Elton R, Reid P. Cannabis, tobacco smoking,
and lung function: a cross-sectional observational study in a general practice population. Br J Gen Pract.
2015;65:e89-e95.
14. Norberg MM, Mackenzie J, Copeland J. Quantifying cannabis use with the timeline followback
approach: a psychometric evaluation. Drug Alcohol Depend. 2012;121:247-252.
15. Lopez-Quintero C, Perez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, et al. Probability
and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine:
results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol
Depend. 2011;115:120-130.
16. Degenhardt L, Glantz M, Bharat C, Peacock A, Lago L, Sampson N, et al. The impact of cohort
substance use upon likelihood of transitioning through stages of alcohol and cannabis use and use
disorder: Findings from the Australian National Survey on Mental Health and Wellbeing. Drug Alcohol
Rev. 2018;37:546-556.
17. Behrendt S, Beesdo-Baum K, Höfler M, Perkonigg A, Bühringer G, Lieb R, et al. The relevance of
age at first alcohol and nicotine use for initiation of cannabis use and progression to cannabis use
disorders. Drug Alcohol Depend. 2012;123:48-56.
18. Hindocha C, Shaban ND, Freeman TP, Das RK, Gale G, Schafer G, et al. Associations between
cigarette smoking and cannabis dependence: a longitudinal study of young cannabis users in the United
Kingdom. Drug Alcohol Depend. 2015;148:165-171.
19. Chen C-Y, O’Brien MS, Anthony JC. Who becomes cannabis dependent soon after onset of use?
Epidemiological evidence from the United States: 2000–2001. Drug Alcohol Depend. 2005;79:11-22.
20. Wagner FA, Anthony JC. From first drug use to drug dependence: developmental periods of risk
for dependence upon marijuana, cocaine, and alcohol. Neuropsychopharmacology. 2002;26:479-488.
21. Degenhardt L, Bharat C, Glantz MD, Sampson NA, Al-Hamzawi A, Alonso J, et al. Association of
Cohort and Individual Substance Use With Risk of Transitioning to Drug Use, Drug Use Disorder, and
Remission From Disorder: Findings From the World Mental Health Surveys. JAMA Psychiatry. 2019.
22. Courtney KE, Mejia MH, Jacobus J. Longitudinal studies on the etiology of cannabis use disorder:
a review. Current addiction reports. 2017;4:43-52.
23. Blanco C, Rafful C, Wall MM, Ridenour TA, Wang S, Kendler KS. Towards a comprehensive
developmental model of cannabis use disorders. Addiction. 2014;109:284-294.
24. Duncan AE, Sartor CE, Scherrer JF, Grant JD, Heath AC, Nelson EC, et al. The association between
cannabis abuse and dependence and childhood physical and sexual abuse: evidence from an offspring of
twins design. Addiction. 2008;103:990-997.
25. Abajobir AA, Najman JM, Williams G, Strathearn L, Clavarino A, Kisely S. Substantiated childhood
maltreatment and young adulthood cannabis use disorders: A pre-birth cohort study. Psychiatry Res.
2017;256:21-31.
26. Grant B, Chu A, Sigman R, Amsbary M, Kali J, Sugawara Y, et al. National institute on alcohol
abuse and alcoholism national epidemiologic survey on alcohol and related conditions-III (NESARC-III)
source and accuracy statement. Bethesda, MD: NIAAA. 2015.
27. Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. Epidemiology of DSM-5 alcohol
use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III.
JAMA Psychiatry. 2015;72:757-766.
28. U.S. Census Bureau. Poverty: U.S. Department of Commerce. 2016.
29. Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for US adults: national health
interview survey, 2012. Vital and health statistics Series 10, Data from the National Health Survey.
2014:1-161.
30. Substance Abuse and Mental Health Services Administration; Results from the 2013 National
Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-48, HHS Publication No.
(SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.
31. Grant BF, Goldstein RB, Smith SM, Jung J, Zhang H, Chou SP, et al. The Alcohol Use Disorder and
Associated Disabilities Interview Schedule-5 (AUDADIS-5): Reliability of substance use and psychiatric
disorder modules in a general population sample. Drug Alcohol Depend. 2015;148:27-33.
32. Hasin DS, Kerridge BT, Saha TD, Huang B, Pickering R, Smith SM, et al. Prevalence and correlates
of DSM-5 cannabis use disorder, 2012-2013: findings from the National Epidemiologic Survey on Alcohol
and Related Conditions–III. Am J Psychiatry. 2016;173:588-599.
33. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.)
Arlington, VA: American Psychiatric Publishing; 2013.
34. Grant BF, Harford TC, Dawson DA, Chou PS, Pickering RP. The Alcohol Use Disorder and
Associated Disabilities Interview schedule (AUDADIS): reliability of alcohol and drug modules in a general
population sample. Drug Alcohol Depend. 1995;39:37-44.
35. Hasin DS, Greenstein E, Aivadyan C, Stohl M, Aharonovich E, Saha T, et al. The Alcohol Use
Disorder and Associated Disabilities Interview Schedule-5 (AUDADIS-5): Procedural validity of substance
use disorders modules through clinical re-appraisal in a general population sample. Drug Alcohol
Depend. 2015;148:40-46.
36. Le Strat Y, Dubertret C, Le Foll B. Impact of age at onset of cannabis use on cannabis
dependence and driving under the influence in the United States. Accid Anal Prev. 2015;76:1-5.
37. Hasin DS, Keyes KM, Alderson D, Wang S, Aharonovich E, Grant BF. Cannabis withdrawal in the
United States: results from NESARC. The Journal of clinical psychiatry. 2008;69:1354-1363.
38. Straus MA. Measuring intrafamily conflict and violence: The conflict tactics (CT) scales. Physical
violence in American families: Routledge; 2017. p. 29-48.
39. Bernstein DP, Fink L, Handelsman L, Foote J, Lovejoy M, Wenzel K, et al. Initial reliability and
validity of a new retrospective measure of child abuse and neglect. The American journal of psychiatry.
1994;151:1132.
40. Walker EA, Unutzer J, Rutter C, Gelfand A, Saunders K, VonKorff M, et al. Costs of health care use
by women HMO members with a history of childhood abuse and neglect. Arch Gen Psychiatry.
1999;56:609-613.
41. Myers B, McLaughlin KA, Wang S, Blanco C, Stein DJ. Associations between childhood adversity,
adult stressful life events, and past-year drug use disorders in the National Epidemiological Study of
Alcohol and Related Conditions (NESARC). Psychology of Addictive Behaviors. 2014;28:1117.
42. Jenkins SP. Easy Estimation Methods for Discrete-Time Duration Models. Oxford bulletin of
economics and statistics. 1995;57:129-136.
43. Research Triangle Institute. Release 11. Vol 1 and 2. Research Triangle Park NRTI 2012. SLM.
SUDAAN® Statistical Software for Analyzing Correlated Data. 2012.
44. Machin D, Cheung, Y. B., & Parmar, M. . Survival analysis: a practical approach: John Wiley &
Sons; 2006.
45. Zeisser C, Thompson K, Stockwell T, Duff C, Chow C, Vallance K, et al. A ‘standard joint’? The role
of quantity in predicting cannabis-related problems. Addiction Research & Theory. 2012;20:82-92.
46. Walden N, Earleywine M. How high: quantity as a predictor of cannabis-related problems. Harm
Reduct J. 2008;5:20.
47. Moss HB, Chen CM, Yi H-Y. Measures of substance consumption among substance users, DSM-IV
abusers, and those with DSM-IV dependence disorders in a nationally representative sample. J Stud
Alcohol Drugs. 2012;73:820-828.
48. Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet.
2009;374:1383-1391.
49. Jouanjus E, Leymarie F, Tubery M, Lapeyre‐Mestre M. Cannabis‐related hospitalizations:
unexpected serious events identified through hospital databases. Br J Clin Pharmacol. 2011;71:758-765.
50. Becker JB, Hu M. Sex differences in drug abuse. Front Neuroendocrinol. 2008;29:36-47.
51. Blanco C, Hasin DS, Petry N, Stinson FS, Grant BF. Sex differences in subclinical and DSM-IV
pathological gambling: results from the National Epidemiologic Survey on Alcohol and Related
Conditions. Psychol Med. 2006;36:943-953.
52. Hernandez-Avila CA, Rounsaville BJ, Kranzler HR. Opioid-, cannabis-and alcohol-dependent
women show more rapid progression to substance abuse treatment. Drug Alcohol Depend. 2004;74:265-
272.
53. Khan SS, Secades-Villa R, Okuda M, Wang S, Pérez-Fuentes G, Kerridge BT, et al. Gender
differences in cannabis use disorders: results from the National Epidemiologic Survey of Alcohol and
Related Conditions. Drug Alcohol Depend. 2013;130:101-108.
54. Mann K, Ackermann K, Croissant B, Mundle G, Nakovics H, Diehl A. Neuroimaging of gender
differences in alcohol dependence: are women more vulnerable? Alcoholism: Clinical and Experimental
Research. 2005;29:896-901.
55. Gómez-Coronado N, Sethi R, Bortolasci CC, Arancini L, Berk M, Dodd S. A review of the
neurobiological underpinning of comorbid substance use and mood disorders. J Affect Disord.
2018;241:388-401.
56. Feingold D, Livne O, Rehm J, Lev‐Ran S. Probability and correlates of transition from cannabis
use to DSM‐5 cannabis use disorder: Results from a large‐scale nationally representative study. Drug
and alcohol review. 2020.
57. Macleod J, Copeland L, Hickman M, McKenzie J, Kimber J, De Angelis D, et al. The Edinburgh
Addiction Cohort: recruitment and follow-up of a primary care based sample of injection drug users and
non drug-injecting controls. BMC Public Health. 2010;10:101.
58. Ensminger ME, Juon H-S, Green KM. Consistency between adolescent reports and adult
retrospective reports of adolescent marijuana use: explanations of inconsistent reporting among an
African American population. Drug Alcohol Depend. 2007;89:13-23.
59. van der Pol P, Liebregts N, de Graaf R, Korf DJ, van den Brink W, van Laar M. Three-year course
of cannabis dependence and prediction of persistence. Eur Addict Res. 2015;21:279-290.
60. Paulhus DL, Reid DB. Enhancement and denial in socially desirable responding. J Pers Soc
Psychol. 1991;60:307.
61. Tourangeau R, Yan T. Sensitive questions in surveys. Psychol Bull. 2007;133:859-883.
62. Di Forti M, Quattrone D, Freeman TP, Tripoli G, Gayer-Anderson C, Quigley H, et al. The
contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a
multicentre case-control study. The Lancet Psychiatry. 2019.
63. Feingold. D, Weiser M, Rehm J, Lev-Ran S. The Association between Cannabis Use and Mood
Disorders: a Longitudinal Study. J Affect Disord. 2015;172:211-218.
64. Feingold D, Weiser M, Rehm J, Lev-Ran S. The association between cannabis use and anxiety
disorders: Results from a population-based representative sample. Eur Neuropsychopharmacol.
2016;26:493-505.
65. Silins E, Horwood LJ, Patton GC, Fergusson DM, Olsson CA, Hutchinson DM, et al. Young adult
sequelae of adolescent cannabis use: an integrative analysis. Lancet Psychiatry. 2014;1:286-293.
66. Nance R, Delaney J, McEvoy JW, Blaha MJ, Burke GL, Navas-Acien A, et al. Smoking intensity
(pack/day) is a better measure than pack-years or smoking status for modeling cardiovascular disease
outcomes. J Clin Epidemiol. 2017;81:111-119.
67. Kerr WC, Stockwell T. Understanding standard drinks and drinking guidelines. Drug and alcohol
review. 2012;31:200-205.
68. López-Pelayo H, Batalla A, Balcells M, Colom J, Gual A. Assessment of cannabis use disorders: a
systematic review of screening and diagnostic instruments. Psychol Med. 2015;45:1121-1133.
69. Lennox R, Dennis ML, Scott CK, Funk R. Combining psychometric and biometric measures of
substance use. Drug Alcohol Depend. 2006;83:95-103.