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Ever heard of a tolerance break? What about cannabinoid hyperemesis syndrome?

Cannabis legalization is spreading across U.S. states, and there is no shortage of questions that people want answered. Practically speaking, cannabis consumption is likely to rise with the social stigma and legal dogma removed.

“You have more people than ever who are exposed to cannabis use,” noted Adie Wilson-Poe, who has spent more than a decade studying the body's endocannabinoid system.

Wilson-Poe helped Weedmaps News answer five key questions on people's minds lately.

Is Cannabis Addictive?

According to Wilson-Poe, who researched the pain management properties of cannabis at the Washington University School of Medicine, cannabis activates Cannabinoid 1 (CB1) receptors in the brain's reward pathway. The Cannabinoid 1 Receptor is a protein-coupled cannabinoid receptor expressed in the peripheral nervous system and central nervous system that is activated by endocannabinoids.

“This activity triggers neurological responses that increase the probability that a person will use it again,” Wilson-Poe said. This process is called “reward.”

Let's face it, cannabis is a rewarding substance, and we feel good when we use it. This is partially thanks to the neurotransmitter dopamine, Wilson-Poe said. There is no shortage of rewarding activities and substances that can be experienced in daily life: alcohol, sugar, gambling, shopping, and more. All things that are pleasurable to an individual affect their brain's reward pathways.

“Anything that creates reward can be abused,” Wilson-Poe said. “The real question here is 'What is the relative addiction liability that cannabis has, compared to other substances?' It is less addictive than nicotine, alcohol and other drugs of abuse.

What do the terms psychoactive and intoxicating mean?

Any substance that affects the function of the brain is considered psychoactive. A change in brain activity can come in many forms, such as the drowsiness of an antihistamine, the relaxation of a benzodiazepine, or the sedation of anesthesia.

“Intoxication is an altered state of consciousness whereby an individual experiences an impairment in their physical and/or mental functioning,” Wilson-Poe said.

It should also be noted that not all psychoactive substances produce intoxication — CBD is a perfect example — but all intoxicants are psychoactive, she added.

What is Cannabis Use Disorder?

Cannabis use disorder (CUD) is most easily described as “an impaired or loss of control despite harmful or adverse effects.”

According to the study in the journal of  “Marijuana Addictive Disorders: DSM-5 Substance-Related Disorders,” a person exhibiting at least two of following criteria in a 12-month period, may be experiencing CUD:

  • Cannabis is often taken in larger amounts over a longer period than was intended.
  • A great deal of time is spent in activities necessary to obtain cannabis, use cannabis or recover from its effects.
  • A consumer has a craving or a strong desire or urge to use cannabis.
  • Recurrent cannabis use results in a failure to fulfill major role obligations at work, school, or home.
  • Cannabis use continues despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.
  • Important social, occupational, or recreational activities are given up or reduced because of cannabis use.
  • Cannabis is recurrently used in situations that are physically hazardous.
  • Cannabis use is continued despite knowledge of having persistent or recurrent physical or psychological problems that are unlikely to have been caused or exacerbated by cannabis.
  • Tolerance, as defined by either a need for markedly increased amounts of cannabis to achieve intoxication and desired effect, or a markedly diminished effect with continued use of the same amount of cannabis.
  • Withdrawal, as manifested by either the characteristic withdrawal symptoms for cannabis, or when a closer related substance is taken to relieve or avoid withdrawal symptoms.

What is Cannabinoid Hyperemesis Syndrome?

“Hyperemesis is defined as cyclic episodes of nausea and vomiting, brought on by chronic cannabis use,” Wilson-Poe said. “For a while, people suspected that pesticides or fertilizers were responsible for this cycle of nausea and vomiting, but more recent and thorough work strongly supports that it is indeed caused by too many cannabinoids in the body.”

Stopping cannabis use is the most effective treatments for hyperemesis. And the best method for treating acute nausea is a hot bath or shower, or the application of topical capsaicin, according to Wilson-Poe.

“Heat and capsaicin both activate the TRPV1 receptor — the transient receptor potential cation channel subfamily V member 1 is a protein encoded by the TRPV1 gene — which plays a major role in the endogenous cannabinoid system,” she said.

What Is a 'Tolerance Break' and What Are the Benefits?

Excessive cannabis use can result in tolerance buildup. It's the same as with numerous substances, such as alcohol. A substance loses its ability to produce the desired effects with repeated use. The solution to this is to 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 reporting in 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 expressed in the peripheral nervous system and central nervous system that 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 states. “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 re-sensitize 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."

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