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Adult-use marijuana legalization continues to spread state by state, and with that change comes growing concerns about cannabis use disorder (CUD).

It would make sense if there's a rise in CUD incidences or at least concern about CUD. Practically speaking, if more people consume cannabis with the threat of jail or punishment removed, a proportionate rise in CUD seems logical.

“You have more people than ever who are exposed to cannabis use,” said Adie Wilson-Poe, Ph.D., a neuroscientist and instructor at Washington University in St. Louis and a subject matter expert for Weedmaps. “We probably will see rates of CUD going up if we don't talk about minimizing tolerance. This is ultimately the thing that we can learn that we did wrong with alcohol, that we did wrong with opioids, that we have a chance to do right here.”

The “right thing” to do for CUD may be to take a tolerance break.

“A tolerance break is going to prevent physical dependence, and physical dependence is a crucial factor of cannabis use disorder,” Wilson-Poe said.

What Is Cannabis Use Disorder?

CUD is often described as “an impaired or loss of control despite harmful or adverse effects,” a definition that sounds a lot like addiction.

“Cannabis activates CB1 receptors in the brain's reward pathway,” Wilson-Poe said. “This activity triggers neurological responses that increase the probability that a person will use it again.”

According to Wilson-Poe, this process is called “reward.” It's difficult to argue that cannabis isn't a rewarding substance. We feel good when we use it. This is partially thanks to the neurotransmitter dopamine, Wilson-Poe explained. There are no shortage of rewarding activities and substances that can be experienced in daily life: alcohol, sugar, gambling, shopping.

“Anything that creates reward can be abused,” Wilson-Poe said.

Will Consuming More Increase My Tolerance?

Excessive cannabis use can lead to tolerance buildup, just like with numerous other substances. A substance loses its ability to produce the desired effects with repeated use.

There's a simple solution to this. Reduce tolerance with periodic breaks in consumption, also called “tolerance breaks.”

“Although scientists don't fully understand the mechanisms of tolerance, there is some evidence which shows that the CB1 receptor expression is diminished in chronic cannabis users, and that abstaining from use for 48 hours is sufficient to bring their expression levels back up to those that are no different from cannabis-naive people,” Wilson-Poe said.

Scientists conducting a 2015 study, “Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects After Abstinence From Cannabis,” found that cannabis dependence is associated with CB1R “downregulation,” which begins to reverse rapidly on termination of cannabis use and may continue to increase over time.

CB1R is a protein-coupled cannabinoid receptor, which is expressed in the peripheral nervous system and central nervous system and is activated by endocannabinoids.

“These group differences in CB1R availability were no longer evident after just two days of monitored abstinence from cannabis,” the study stated. “There was a robust negative correlation between CB1R availability and withdrawal symptoms after two days of abstinence.”

Taking tolerance breaks offers numerous benefits, according to Wilson-Poe.

“For patients, it allows them to resensitize their bodies so that they can prevent dose escalation (steadily increasing their consumption),” she said. “Preventing dose escalation not only saves patients money, but it is also is key to preventing the body from developing a physical dependence upon cannabis – people experience withdrawal symptoms if they stop using.”

Potency may also be a factor in CUD. A 2018 study shows a correlation between higher potencies and the progression of the first symptoms of CUD. The study,Higher average potency across the United States is associated with progression to first cannabis use disorder symptom,” shows that people using cannabis at a national average 4.9 percent THC were at nearly twice the risk for developing the first CUD symptom within a year.  

“This study provides prospective evidence suggesting higher potency cannabis, on average in the U.S., increases risk for onset of first cannabis use disorder symptom,” the study concluded. “Development of guidelines regarding cannabis potency is critical for reducing the costs associated with negative health outcomes.”

Those who use tobacco and cannabis should take note of a study set to be published later in 2019. The study in the Journal of Substance Abuse Treatment, “Sequential and simultaneous treatment approaches to cannabis use disorder and tobacco use,” shows that quitting tobacco may be beneficial for those seeking to quit cannabis. Results of the study show “tobacco cessation outcomes generally were poor.”

Can Cannabinoids Help?

Stopping cannabis use isn't without hazards. Nearly one-third of regular cannabis users report withdrawal symptoms when stopping after prolonged use, a new study showed. The symptoms listed include irritability, insomnia, decreased appetite, depressed mood, anxiety, and restlessness.

The figures are worse for highly dependent users. The incidence of withdrawal can reach up to 50 to 95 percent of individuals, according to the study. However, cannabinoids may be a promising group of drugs to treat cannabis withdrawal symptoms, as shown in the study “A Systematic Review of the Efficacy of Cannabinoid Agonist Replacement Therapy for Cannabis Withdrawal Symptoms.” The study showed these medications may help decrease the rate of relapse in the treatment of cannabis dependence due to withdrawal symptoms occurring within the first few weeks of treatment.

“Despite the limited number of studies and methodological differences, our findings demonstrate that the use of dronabinol, nabilone, or nabiximols, either alone or in combination with other drugs, shows promise in reducing cannabis withdrawal symptoms, probably with a dose-dependent effect,” the article states. “This has also been considered a safe group of medications with good tolerability and few adverse effects.”

The choice is clear for those who have tolerance buildup: Either escalate consumption or take a break. The study shows that 48 hours might be enough time off, and Wilson-Poe believes some users could find relief from an even lower than dose than was needed before the break. Far less clear is just how long takes to develop tolerance, which she said is “highly variable,” and depends on numerous factors.

For example, someone taking 5 milligrams or 10 milligrams of THC in oral form at night before sleeping will develop tolerance rapidly because they won't notice the effects of the high doses because they are sleeping. Someone who only takes a few puffs of marijuana a day, on the other hand, will take longer to develop tolerance, Wilson-Poe said.

“The only thing that is universal among people is if you notice it does not do what it used to do, you've got tolerance,” she said.

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