Cannabis use


Cannabis use

Cannabis is a generic term used to denote the several psychoactive preparations of the plant Cannabis sativa. The major psychoactive consituent in cannabis is ∆-9 tetrahydrocannabinol (THC). Compounds which are structurally similar to THC are referred to as cannabinoids.

In addition, a number of recently identified compounds that differ structurally from cannabinoids nevertheless share many of their pharmacological properties. The Mexican term 'marijuana' is frequently used in referring to cannabis leaves or other crude plant material in many countries. The unpollinated female plants are called hashish.

Cannabis oil (hashish oil) is a concentrate of cannabinoids obtained by solvent extraction of the crude plant material or of the resin.

Cannabis is by far the most widely cultivated, trafficked and abused illicit drug. Half of all drug seizures worldwide are cannabis seizures. The geographical spread of those seizures is also global, covering practically every country of the world. About 147 million people, 2.5% of the world population, consume cannabis (annual prevalence) compared with 0.2% consuming cocaine and 0.

2% consuming opiates. In the present decade, cannabis abuse has grown more rapidly than cocaine and opiate abuse. The most rapid growth in cannabis abuse since the 1960s has been in developed countries in North America, Western Europe and Australia. Cannabis has become more closely linked to youth culture and the age of initiation is usually lower than for other drugs.

An analysis of cannabis markets shows that low prices coincide with high levels of abuse, and vice versa. Cannabis appears to be price-inelastic in the short term, but fairly elastic over the longer term.

Though the number of cannabis consumers is greater than opiate and cocaine consumers, the lower prices of cannabis mean that, in economic terms, the cannabis market is much smaller than the opiate or cocaine market.

The acute effects of cannabis use has been recognized for many years, and recent studies have confirmed and extended earlier findings. These may be summarized as follows:

  • Cannabis impairs cognitive development (capabilities of learning), including associative processes; free recall of previously learned items is often impaired when cannabi is used both during learning and recall periods;
  • Cannabis impairs psychomotor performance in a wide variety of tasks, such as motor coordination, divided attention, and operative tasks of many types; human performance on complex machinery can be impaired for as long as 24 hours after smoking as little as 20 mg of THC in cannabis; there is an increased risk of motor vehicle accidents among persons who drive when intoxicated by cannabis.
  • selective impairment of cognitive functioning which include the organization and integration of complex information involving various mechanisms of attention and memory processes;
  • prolonged use may lead to greater impairment, which may not recover with cessation of use, and which could affect daily life functions;
  • development of a cannabis dependence syndrome characterized by a loss of control over cannabis use is ly in chronic users;
  • cannabis use can exacerbate schizophrenia in affected individuals;
  • epithetial injury of the trachea and major bronchi is caused by long-term cannabis smoking;
  • airway injury, lung inflammation, and impaired pulmonary defence against infection from persistent cannabis consumption over prolonged periods;
  • heavy cannabis consumption is associated with a higher prevalence of symptoms of chronic bronchitis and a higher incidence of acute bronchitis than in the non-smoking cohort;
  • cannabis used during pregnancy is associated with impairment in fetal development leading to a reduction in birth weight;
  • cannabis use during pregnancy may lead to postnatal risk of rare forms of cancer although more research is needed in this area.

The health consequences of cannabis use in developing countries are largely unknown beacuse of limited and non-systematic research, but there is no reason a priori to expect that biological effects on individuals in these populations would be substantially different to what has been observed in developed countries. However, other consequences might be different given the cultural and social differences between countries.

Several studies have demonstrated the therapeutic effects of cannabinoids for nausea and vomiting in the advanced stages of illnesses such as cancer and AIDS. Dronabinol (tetrahydrocannabinol) has been available by prescription for more than a decade in the USA.

Other therapeutic uses of cannabinoids are being demonstrated by controlled studies, including treatment of asthma and glaucoma, as an antidepressant, appetite stimulant, anticonvulsant and anti-spasmodic, research in this area should continue.

For example, more basic research on the central and peripheral mechanisms of the effects of cannabinoids on gastrointestinal function may improve the ability to alleviate nausea and emesis.

More research is needed on the basic neuropharmacology of THC and other cannabinoids so that better therapeutic agents can be found.


Professor explores marijuana’s safe use and addiction

Cannabis use

GAZETTE: Is it that there are myths that haven’t been dispelled yet, either by widespread experience or by scientific findings?

HILL: The myths have been disproven. Unfortunately, the loudest voices in the cannabis debate often are people who have political or financial skin in the game, and the two sides are entrenched.

Pro-cannabis people will say that cannabis is the greatest medication ever, and harmless. Others — often in the same field that I’m in, people who treat patients, people who do research with cannabis — will at times misrepresent the facts as well.

They will go into a room of 100 or 200 high schoolers and relay the message that cannabis is as dangerous as fentanyl. That’s not true either. These camps seem to feel that even a single shred of evidence that runs counter to their narrative hurts them.

So at the end of the day, a lot of what people hear about cannabis is either incomplete or flat-out wrong because both sides are promoting polar opposite views of cannabis.

GAZETTE: What is an example of these myths?

HILL: I think the greatest example is when you talk about the addictive nature of cannabis. You can become addicted to cannabis, though most people don’t.

Yet invariably, when people hear about what I do, they say, “Oh, you’re an addiction psychiatrist? Well, cannabis is not physically addictive; it’s psychological.” So there are fallacies about cannabis.

And they continue because people are invested in trying to get people to vote one way or another on issues medical cannabis or legalization of recreational cannabis. That is a major problem.

Every single day we have patients come in who are interested in using cannabis as a medication or they’re using it recreationally or are interested in cannabidiol, and they have beliefs about cannabis that they’ve held for years that aren’t true. And that becomes a major barrier. It’s hard to dispel those beliefs in the office.

GAZETTE: What is cannabis addiction ?

HILL: It’s less addictive than alcohol, less addictive than opioids, but just because it’s less addictive doesn’t mean that it’s not addictive. There’s a subset of people — whom I treat frequently — who are using cannabis to the detriment of work, school, and relationships.

It’s hard for the majority of people — who may use once a month or once every six months, or they tried it in Vegas because it’s legal there — to recognize the reality that there are many people who are using and losing in key areas of their lives. I’ve had patients who have lost multimillion-dollar careers.

It’s hard for people to understand that that can happen. I often compare cannabis to alcohol. They’re very similar in that most people who use never need to see somebody me. But the difference is that we all recognize the dangers of alcohol.

If you go into a room of 200 high school kids, they know it’s dangerous and binge drinking among high schoolers is way down. But if you ask that same group about cannabis, you’re going to get all different answers.

Data that suggests that although cannabis use among young people is flat — that’s another misrepresentation, that it’s going up — the perception of risk among those young people is going down. So, while everyone’s talking about it, and stores are opening in Brookline, in Leicester, and all over the state, adults and young people are not clear about the risks.

GAZETTE: What about the other side, myths about cannabis’ harms?

HILL: How are things misrepresented by anti-cannabis crusaders? They tend to ignore the idea that dose matters.

When we talk about the harms of cannabis, young people using regularly can have cognitive problems, up to an eight-point loss of IQ over time. It can worsen depression. It can worsen anxiety. But all of those consequences depend upon the dose.

The data that shows those impacts look at young people who are using pretty much every day. They’re heavy users who usually meet criteria for cannabis-use disorder.

So when people who are opposed to cannabis talk about those harms, they don’t mention that they’re talking about heavy users. The 16-year-old kid who uses once or twice a week, I’d still be worried about it, but that use has not been correlated to these harms.

“It’s less addictive than alcohol, less addictive than opioids, but just because it’s less addictive doesn’t mean that it’s not addictive.”

GAZETTE: What constitutes heavy use?

HILL: Cannabis is different than alcohol, because with alcohol, you can use once a week, three times a week, and it can be a problem. You can have eight drinks once a week and get into a whole bunch of trouble.

Cannabis is a little different in the sense that the people who run into trouble are using it pretty much every day, multiple times a day for the most part.

That’s how this less-harmful, less-addictive substance turns into something that’s very harmful for them.

GAZETTE: Are the characteristics of cannabis addiction common to other types of addiction?

HILL: They are. When someone’s sitting in my office, if you redacted some of the details of their story, it’d be hard to tell who’s got which problem: alcohol versus opioids versus cannabis. The onset — what will bring you into my office — is different. People who are using cannabis are not going to knock off a CVS to fuel their habit.

If somebody’s using fentanyl, they may overdose and that could be potentially fatal. That’s not going to happen with cannabis. But when you talk to them, other details are often the same. “My wife said I gotta come talk to you or she’s gonna kick me out.” And that can happen to somebody who’s drinking, that could happen to somebody using opioids.

It’s not as dramatic if cannabis is the drug of choice, but once somebody meets the criteria for a cannabis-use disorder or alcohol-use disorder or opioid-use disorder, there are a lot of similarities, more similarities than differences, frankly.

One unique thing about cannabis is that on the same day, I may have somebody who is 26, smoking four times a day, graduated from a local elite university, and not making it they want to be making it. Then, the next hour, I may see a 70-year-old woman who has chronic back issues and tried multiple medications, multiple injections, and wants to use cannabis for her pain.

There aren’t a lot of doctors who see both of these patients and that is one of the reasons why people take really strong positions, when in fact many of the answers on cannabis are down the middle. There are a lot of things we don’t know, and a lot of answers we wouldn’t have expected. I’ve done studies myself where I hypothesized one thing, and something else comes out.

Are you going to dismiss that or let that new information shape what you think about cannabis? You have to be open-minded in an area that is continuing to evolve. If you aren’t open-minded and willing to have a sensible conversation about cannabis, you won’t be able to reach your patients.

A lot of times patients don’t tell their primary care doctor about their cannabis use, their use of CBD, because they think their physician won’t approve of their use. That’s another major problem. If you’re using CBD to treat a given medical condition and your doctor doesn’t know it and you’ve got six other medications, that could be a major issue.

“When we talk about the harms of cannabis, young people using regularly can have cognitive problems, up to an eight-point loss of IQ over time. It can worsen depression. It can worsen anxiety. But all of those consequences depend upon the dose.”

GAZETTE: We’ve talked about negatives. What is the truth of the positive health benefits?

HILL: We’re conditioned as physicians to believe that cannabis is bad for you, but there is data that it can be useful in certain cases. I would prefer that we use FDA-approved medications when possible. They are much safer, and you can be sure of the purity and potency.

But there is evidence to support the use of cannabis and cannabinoids for a handful of medical conditions. That is dwarfed by the number of conditions for which people are actually using it, but the evidence of benefit is not zero.

To a lot of doctors, it’d be convenient if it was zero so they could tell patients that this whole idea is a sham. Thus, there are physicians who aren’t willing to entertain data demonstrating therapeutic use of cannabis.

I think that’s a missed opportunity because if a patient comes in and says, “I want to use cannabis to treat condition x,” cannabis might not be the best treatment for that condition, but just being willing to engage in a conversation about it, you may get them into treatment they might not otherwise get into.

If they said, “Look, I want to use cannabis to treat my anxiety,” I’m not going to recommend using whole-plant cannabis to treat anxiety, but maybe they haven’t tried cognitive behavioral therapy. Just by having that conversation, you could do a lot of good.

GAZETTE: Is pain one area that cannabis is proven for?

HILL: In 2015, we had two FDA-approved cannabinoids, dronabinol and nabilone, for nausea and vomiting associated with cancer chemotherapy, and for appetite stimulation in wasting conditions. Last year they added cannabidiol — only one version is FDA-approved — and it is for a couple of pediatric epilepsy conditions.

Beyond the FDA-approved indications, the best evidence is for three things: chronic pain, neuropathic pain — which is a burning sensation in your nerves — and muscle spasticity associated with multiple sclerosis. There are more than six randomized control trials for each of those three conditions.

There are problems associated with some of those trials — sample sizes are small and the follow-up periods are not as long as we would them to be.

I wish there was better evidence for chronic pain, but as long as we have a clear conversation about what the risks may be, then to me, there’s enough evidence for those three things to think about cannabis or cannabinoids not as first-line or second-line treatments but as third-line treatments.

GAZETTE: The House Judiciary Committee recently approved a bill removing cannabis as a Schedule 1 controlled substance. There’s a long way to go with that legislation, but would that step make it easier to conduct the studies that will clear some of the confusion?

HILL: Schedule 1 really means two things. Number one, does it have addictive potential? Cannabis does, clearly. But it also means that there is no medical value. I think you’re hard-pressed at this point to say that cannabis and cannabinoids have no medical value.

So I don’t think it should be a Schedule 1 substance and changing that really would make it a lot easier to study. Funding is a bigger barrier. I’m sitting in a state right now that is profiting from cannabis. I’ve got a store a mile away from my hospital, and they’re printing money.

It’s raining out, snowing, and there are people lined up outside of the store to buy cannabis. There are permanent crowd-control ropes in the parking lot and a police detail. A lot of people are profiting from cannabis while neglecting to contribute to the scientific evidence base.

It shouldn’t be that way.

GAZETTE: What is most important for the public to know about this?

HILL: Over 22 million Americans used cannabis last year, and the literature says about 10 percent of those are using medicinally. If that’s true, a lot of those people are just talking to physicians who write certifications all day.

That means there isn’t the level of follow-up that should be there; the standard of care is lower than it should be.

I think patients who are interested in cannabinoids should be talking to their own doctors about it, because ideally, their physician should be the one helping them think through the risks and benefits.

GAZETTE: With cannabis legalized recreationally, why shouldn’t people interested in it as a medicine just say, “Well, I’ll go buy some”?

HILL: That question opens the door to the poor job we’ve done educating people about cannabis. A lot of people want to try it, but they’re not educated about how it works. They don’t know what the typical dose is or the onset of action with edibles.

The number of ED visits has gone up. People may say, “Oh, there is a store on Route 9. I’m going to go. I never tried it before.” And, whether they’re in Las Vegas or Colorado or someplace else, they repeat the same mistakes.

They’re not going to have a fatal overdose, but they can get very sick and that should never happen.

GAZETTE: So, if you have a glass of alcohol, you know roughly what the effect might be on your body. But for a particular dose of pot, we have no clue?

HILL: Less of a clue. A typical brownie has 100 milligrams of THC, but a typical serving size is 10 milligrams. I don’t know about you, but when I’m eating a brownie, I eat the whole brownie.

So, it’s the idea that if you’re going to use an edible and you’re buying a brownie then you’re going to consume a tenth of it, or if you eat cannabis, it’s going to take longer than if you were to smoke it.

Some people will take a bite of an edible and nothing happens, so they take another bite. A half-hour later, they’ve got four or five times the typical dose. So long as you know that, you’re not going to have an issue.

But if you’re not aware of that and you have more, if you’ve never used it before, 40 to 50 milligrams of THC is going to knock you for a loop. So if you’re going to use recreationally or medically, you need to be educated about what you’re doing.

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Know the Risks of Marijuana

Cannabis use

Marijuana is the most commonly used illegal substance in the U.S. and its use is growing. Marijuana use among all adult age groups, both sexes, and pregnant women is going up. At the same time, the perception of how harmful marijuana use can be is declining. Increasingly, young people today do not consider marijuana use a risky behavior.

But there are real risks for people who use marijuana, especially youth and young adults, and women who are pregnant or nursing. Today’s marijuana is stronger than ever before. People can and do become addicted to marijuana.

Marijuana Risks

Marijuana use can have negative and long-term effects:

Brain health: Marijuana can cause permanent IQ loss of as much as 8 points when people start using it at a young age. These IQ points do not come back, even after quitting marijuana.

Mental health: Studies link marijuana use to depression, anxiety, suicide planning, and psychotic episodes. It is not known, however, if marijuana use is the cause of these conditions.

Athletic Performance: Research shows that marijuana affects timing, movement, and coordination, which can harm athletic performance.

Driving: People who drive under the influence of marijuana can experience dangerous effects: slower reactions, lane weaving, decreased coordination, and difficulty reacting to signals and sounds on the road.

Baby’s health and development: Marijuana use during pregnancy may cause fetal growth restriction, premature birth, stillbirth, and problems with brain development, resulting in hyperactivity and poor cognitive function. Tetrahydrocannabinol (THC) and other chemicals from marijuana can also be passed from a mother to her baby through breast milk, further impacting a child’s healthy development.

Daily life: Using marijuana can affect performance and how well people do in life. Research shows that people who use marijuana are more ly to have relationship problems, worse educational outcomes, lower career achievement, and reduced life satisfaction.

What is Your Marijuana IQ?

How much do you really want to know about the risks of marijuana? You might be surprised.» Take the Quiz

Marijuana Addiction

Contrary to popular belief, marijuana is addictive. Research shows that:

  • 1-in-6 people who start using the drug before the age of 18 can become addicted.
  • 1-in-10 adults who use the drug can become addicted.

Over the past few decades, the amount of THC in marijuana has steadily climbed; today's marijuana has three times the concentration of THC compared to 25 years ago.

The higher the THC amount, the stronger the effects on the brain—ly contributing to increased rates of marijuana-related emergency room visits.

While there is no research yet on how higher potency affects the long-term risks of marijuana use, more THC is ly to lead to higher rates of dependency and addiction.

About Marijuana

Marijuana refers to the dried leaves, flowers, stems, and seeds from the Cannabis sativa or Cannabis indica plant. Marijuana is a psychoactive drug that contains close to 500 chemicals, including THC, a mind-altering compound that causes harmful health effects.

People smoke marijuana in hand-rolled cigarettes, in pipes or water pipes, in blunts, and by using vaporizers that pull THC from the marijuana. Marijuana can also be mixed in food (edibles), such as brownies, cookies, and candy, or brewed as a tea. People also smoke or eat different forms of marijuana extracts, which deliver a large amount of THC and can be potentially more dangerous.

Rise of Marijuana Use

Today, marijuana use is on the rise among all adult age groups, both sexes, and pregnant women. People ages 18-25 have the highest rate of use.

Marijuana and THC remain illegal at the federal level, even though many states have legalized its use. In states where legal, marijuana is a fast-growing industry with sales to individuals over 21 in retail stores, wineries, breweries, coffee shops, dispensaries, online, as well as grown at home.

Cannabis – Alcohol and Drug Foundation

Cannabis use

Cannabis can be smoked, eaten or vaporized and comes in different forms. Users report that the subjective effects of cannabis vary significantly depending on the form consumed.2

  • Marijuana − the dried leaves and flowers (buds) of the cannabis plant that are smoked in a joint or a bong. This is the most common form.
  • Hashish – the dried plant resin that is usually mixed with tobacco and smoked or added to foods and baked; such as cookies and brownies.
  • Hash oil – liquid that is usually used sparingly (due to high potency) and added to the tip of a joint or cigarette and smoked.1
  • Concentrates – extracts (dabs, wax or shatter) typically using butane hash oil as a solvent, often vaporised in small quantities due to high THC content.1

Cannabis can be prepared into various foods generally called ‘edibles’. It takes between 1-3 hours to feel the effects after eating cannabis.

2 Impatient or naïve users may believe they have not taken enough to feel the effects, and if they consume more they may find later that the psychoactive effects are unpleasantly strong. When edible products have inconsistent levels of THC even experienced users may find it difficult to regulate the amount consumed.

When smoked or vaporised, the effects are usually felt straight away.3 There are health concerns about the impact of smoking, especially in the long term, especially if mixed with tobacco.

Cannabis can also come in synthetic form, which may be more harmful than real cannabis.

Effects of cannabis

There is no safe level of drug use. Use of any drug always carries some risk. It’s important to be careful when taking any type of drug.

Cannabis affects every individual differently. Even the same person may have a different experience on separate occasions or over the course of their life. Some of the factors that influence these differences appear to be:3,4

  • size, weight and health
  • whether the person is used to taking it
  • whether other drugs are taken around the same time
  • the amount taken
  • the strength of the drug
  • expectations of consuming cannabis
  • the environment of the individual
  • the individual’s personality.

The effects of cannabis vary between people, and may even be different for the same person at different times. Some people report feelings of relaxation and euphoria while other people report experiences of anxiety and paranoia.4

The effects of cannabis may be felt immediately if smoked, or within an hour or two if eaten and effects may include:3,4

  • feelings of relaxation and euphoria
  • spontaneous laughter and excitement
  • increased sociability
  • increased appetite
  • dry mouth.

If large amount, strong batch, or concentrated form is consumed, you may be more ly to also experience:2,3,4

  • memory impairment
  • slower reflexes
  • bloodshot eyes
  • increased heart rate
  • mild anxiety and paranoia.

Long-term effects

Long-term effects are dependent on how much and how often the cannabis is consumed and may also be affected by how the cannabis is consumed (e.g. vaporising a concentrate versus smoking the flower).2 Heavy, regular use of cannabis may eventually cause:5,6

  • tolerance to the effects of cannabis
  • dependence on cannabis
  • reduced cognitive functioning.

Smoking cannabis may increase the lihood of experiencing:

  • sore throat
  • asthma
  • bronchitis
  • if smoked with tobacco, cancer.

Those with a family history of mental illness are more ly to also experience anxiety, depression and psychotic symptoms after using cannabis. Psychotic symptoms include delusions, hallucinations and seeing or hearing things that do not exist or are distorted.

Using cannabis with other drugs

The effects of taking cannabis with other drugs − including over-the-counter or prescribed medications − can be unpredictable.

Cannabis +alcohol: nausea, vomiting.4

Cannabis is sometimes used to help with the ‘come down’ effects of stimulant drugs, such as ice, speed and ecstasy.


Giving up cannabis after regular, heavy use over a long time is challenging, because the body has to get used to functioning without it. Withdrawal symptoms may last for only a week, but sleep may be affected for longer. Symptoms include:8

  • anxiety
  • irritability
  • loss of appetite and upset stomach
  • sweating, chills and tremors
  • restless sleep and nightmares.6


Problem Cannabis Use

Cannabis use

As noted above, the literature is unclear on the association between cannabis use and the progression to the sort of cannabis use determined to be “problem” use. A major contributor to this issue is the lack of official distinction between “risky” or “problem” use of cannabis (Casajuana et al., 2016).

In recent years, CUD1 has been termed an official psychiatric disorder (APA, 2013; WHO, 2015). A current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis of CUD replaces the previous diagnoses of cannabis abuse and cannabis dependence.

Although some progress has been made in standardizing terminology, explicit characterizations of cannabis use patterns that precede abuse or dependence still remain unclear (Casajuana et al., 2016).

Given this context, for the purposes of this chapter the committee will use the broad term “problem cannabis use disorder” to encompass various levels of hazardous or potentially harmful cannabis use patterns, including those related to CUD, dependence, and abuse.

The committee did not identify a good- or fair-quality systematic review that reported on the association between cannabis use and cannabis use disorder, dependence, abuse, or problem cannabis use.

Several studies using large population-based surveys have explored the rates of cannabis use disorder and the variables that affect progression from the initiation of use to problem cannabis use.

According to findings from Wave 1 (baseline; 2001–2002) and Wave 2 (follow-up; 2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a survey of a nationally representative sample of U.S.

adults ages 18 years and older (n = 34,653 in Wave 2), cannabis use reported during the first wave was significantly associated with any cannabis use disorder during the second wave (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI] = 6.4–14.1); 14.1 percent of past-year cannabis users in Wave 1 met the criteria for cannabis abuse in Wave 2, and 5.

1 percent met criteria for dependence, as compared with 0.7 percent of participants who reported no past-year cannabis use during Wave 1 who met the criteria for cannabis abuse and 0.2 percent who met the criteria for cannabis dependence (Blanco et al., 2016). This study accounted for multiple sociodemographic factors that may have affected the outcome.

The progression of cannabis use to developing cannabis use disorder as a function of the frequency of cannabis use was also explored using Waves 1 and 2 of the NESARC data (Cougle et al.

, 2016) Among the past-year weekly nondependent cannabis users in Wave 1 (n = 435), 9.

7 percent progressed to cannabis dependence in Wave 2; however, an increased frequency of cannabis use per day only weakly predicted progression of cannabis use to CUD (odds ratio [OR], 1.08; CI = 1.04–1.13) in a prospective analysis.

A cross-sectional analysis of Wave 1 data found that 8.0 percent of respondents who reported using cannabis at least once in the past year met the criteria for dependence, whereas among weekly and daily cannabis smokers, 17.0 percent and 18.8 percent, respectively, met the criteria for dependence.

Using data obtained from the U.S. National Household Survey on Drug Abuse (NHSDA) conducted in 2001 with a representative sample of U.S. residents 12 years of age and older (n = 114,241), Chen and colleagues (2005) explored the rates of developing cannabis dependence syndrome after onset of use.

Of the recent onset users (individuals that used cannabis within 24 months prior to assessment), an estimated 3.9 percent developed dependence during the interval since first use (median time = 1 year). Of those who initiated cannabis use more than 24 months before the assessment, and were also active cannabis users within the past year, 9.

9 percent developed dependence (Chen et al., 2005).

Using data from two large U.S. surveys—the 1991 National Longitudinal Alcohol Epidemiologic Survey (NLAES) (n = 42,862) and the 2002 NESARC (n = 43,093)—Compton and colleagues (2004) assessed the rates of cannabis use disorder as a function of biological sex, ethnicity, and frequency of cannabis use.

They found that the overall prevalence of DSM-IV cannabis abuse and dependence increased significantly from 1.2 percent to 1.5 percent between 1991 and 2001. The greatest increases in these rates were observed among young black men and women (p < 0.001), and young Hispanic men (p = 0.006).

The increase in the rates of cannabis use disorder among cannabis users was observed in the absence of self-reported increases in frequency or quantity of use (p = 0.

002); this suggests that the increases in cannabis use disorders may be due to the increased potency (percent tetrahydrocannabinol [THC]) of cannabis between 1991 and 2001.

The limitations of these studies include the reliance on self-reported cannabis use, the fact that data were restricted to two time points of assessment separated by 3 years, and that the findings are epidemiological data obtained more than 10 years ago.

A significant issue with relying on self-report methodologies to ascertain problem cannabis use is that this requires that the respondent have insight into the fact that cannabis is actually causing problems in order to meet criteria for cannabis abuse/dependence (as per the DSM-IV) or CUD (as per the DSM-V).

Furthermore, while the primary literature indicates a weak association between the frequency of use and a greater risk of developing cannabis use disorder, it should be noted that the frequency of use in these studies was assessed in the absence of determining the amount of cannabis used per occasion, which is a primary variable hypothesized to affect the rates of developing problem cannabis use.

Cannabis use is increasing across the country and across age groups (Hasin et al., 2015); the strength of cannabis has increased (ElSohly et al., 2016); and different routes of cannabis administration have become popular, including vaping, dabs, and edibles (Daniulaityte et al., 2015; Kilmer et al., 2013; Pacula et al., 2016).

These trends may reflect an increased vulnerability to developing problem cannabis use relative to what was estimated the Wave 1 and Wave 2 NESARC data collected in 2001–2001 and 2004–2005. Therefore, the estimated risk of developing problem cannabis use these data may not accurately reflect the risk now, given the current trends.

CONCLUSION 13-1 There is substantial evidence for a statistical association between increases in cannabis use frequency and the progression to developing problem cannabis use.

Systematic ReviewsKedzior and Laeber (2014) searched two large databases for articles published from inception through 2013 to identify studies of cannabis use and anxiety.

They included cross-sectional and longitudinal studies conducted in noninstitutionalized populations, with anxiety diagnoses DSM or International Classification of Diseases (ICD) criteria, odds ratios, or data sufficient for the calculation of a measure of effects, and they included comparison data from healthy nonusers.

Their purpose was to examine both of the possible temporal relationships between cannabis use and anxiety (i.e., the effect of anxiety on cannabis use and the effect of cannabis use on anxiety). They identified 31 studies for their review.

Five of these examined cannabis use at baseline and anxiety at follow-up, and the remainder considered the role of anxiety as a risk factor for cannabis use. Sample sizes were almost 2,000 or greater in four studies and more than 12,000 in a fifth study.

After analyzing various subsets of the selected articles, the authors concluded that there was a small positive association between anxiety and CUD (OR, 1.68; 95% CI = 1.23–2.31, n = 13 studies). One study included in the analysis assessed anxiety at baseline and cannabis use at follow-up and did not find an association (OR, 0.94; 95% CI = 0.86–1.

03), but it did not report on problem cannabis use at follow-up. The authors found little evidence of publication bias after their assessment, and they reported a moderate-high heterogeneity. They offered three possible explanations of this heterogeneity: differences in adjustment for confounding when calculating the OR, year of publication, and different methods for diagnosing anxiety. this systematic review, it appears that while there is a small association between anxiety and CUD, anxiety does not seem to be a predisposing risk factor for developing CUD.

Primary Literature The committee did not identify any good-quality primary literature that reported on anxiety as a risk or a protective factor for developing problem cannabis use and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.

Systematic ReviewsHumphreys et al. (2013) conducted a systematic literature review and meta-analysis to assess the association between childhood treatment with stimulant medication and later substance use, abuse, or dependence.

They searched the literature published between 1980 and 2012 and included published and unpublished studies with a longitudinal design, binary measures to identify children with attention deficit hyperactivity disorder (ADHD), binary substance use and abuse measures, and data allowing the calculation of odds ratios.

Fifteen studies were included in the review; nine of these evaluated the association of stimulant medication with a lifetime history of ever using marijuana, and nine evaluated the association of stimulant medication with cannabis abuse or dependence.

All study subjects were children at the time of enrollment, and the follow-up time ranged from 4 to 28 years in the group of 9 studies reviewed, with the mean age at follow-up ranging from 15 to 26 years.

One of the studies in this systematic review included children as young as 4 years of age who would not be expected to develop CUD in the follow-up time period. The percentage of study subjects who were male ranged from 0 to 100, with the majority of the studies being more than 80 percent male. The researchers reported an OR of 1.01 (95% CI = 0.

68–1.50) for the association between stimulant medication and marijuana abuse or dependence. Some suggestion of publication bias was noted, and heterogeneity was noted in the group of nine studies with data about marijuana abuse or dependence. These results suggest that medication for ADHD during childhood does not constitute a risk factor for developing problem cannabis use later in life.

Primary Literature The committee did not identify any good-quality primary literature that reported stimulant medication in children diagnosed with ADHD as a risk or a protective factor for developing problem cannabis use and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.

Systematic Reviews The committee did not identify a good- or fair-quality systematic review that reported on psychopathology as a risk or a protective factor for developing problem cannabis use.

Primary Literature Data obtained from the 2001 and 2005 NESARC, a survey of a nationally representative sample of U.S. adults ages 18 years and older (n = 34,653 in Wave 2), explored anxiety as a risk factor for progression to cannabis use disorder.

Using data from Wave 2 (comprised of 34, 653 participants from Wave 1), Feingold and colleagues (2016) found that anxiety disorders were not associated with an increased incidence of cannabis use disorders (aOR, 0.68; 95% CI = 0.41–1.14).

Similarly, a prospective analysis using Wave 1 and Wave 2 NESARC data also found that anxiety disorders failed to predict progression from cannabis use to cannabis dependence in weekly cannabis users (Cougle et al., 2016).