Early marijuana use 'primes' the brain to enjoy cocaine, study suggests

A new study on rats suggests that using marijuana as an adolescent "reprograms the initial behavioral, molecular, and epigenetic response to cocaine."

cannabis plant marijuana
Justin Sullivan - Getty
  • In the study, adolescent and adult rats were first given a synthetic cannabinoid and then cocaine.
  • The results showed that the young rats' brains were more sensitive to the effects of cocaine, but these effects weren't observed in the adult rats.
  • The researchers suggest that research like this can help to develop better treatments for substance abuse disorders.


A new study suggests that using marijuana in your teenage years may prime your brain to respond positively to your first experience with cocaine. The findings offer molecular insight into the question of whether marijuana is a gateway drug. After all, studies have repeatedly shown that having a good first experience with a drug makes you more likely to use it again, and therefore potentially become addicted.

The study is published in the journal PNAS.

"We know from human epidemiological studies that individuals who abuse cocaine have a history of early cannabis use, and that a person's initial response to a drug can have a large impact on whether they continue to use it. But many questions remain on how early cannabis exposure affects the brain," epidemiologist Denise Kandel, PhD, a professor of Sociomedical Sciences in Psychiatry at Columbia's Vagelos College of Physicians and Surgeons and co-senior author of the new study, told Science Daily.

In the study, researchers gave a synthetic psychoactive cannabinoid called WIN 55,212-2 (WIN) to adolescent and adult rats. Then, both groups of rats were given cocaine, and the researchers monitored how the animals responded.

Fig 1. Cross-sensitization between WIN and cocaine in adolescent rats is associated with histone hyperacetylation in the PFC.

Scherma et al.

The results showed that young rats who had been exposed to WIN were more sensitive to the effects of cocaine. This early exposure "reprograms the initial behavioral, molecular, and epigenetic response to cocaine" in young rats. These changes were not observed in adult rats.

Past research has shown that young rats that have been exposed to cannabinoids become "cross-sensitized" to cocaine, and that cross-sensitization can alter the extent to which rats crave cocaine and experience withdrawal symptoms.

The new study took a close look at how cannabinoids prime bodily systems for cocaine.

Changes in the prefrontal cortex

One such system is the endocannabinoid system, which is impaired by the use of cannabis or cannabinoids. Studies have linked impaired endocannabinoid signaling with increased stress responsivity, negative emotional states, and drug craving.

"The endocannabinoid system has a modulatory role in brain reward and cognitive processes," the researchers wrote. "It has been hypothesized that repeated interference with endocannabinoid signaling (e.g., through abuse of cannabis or synthetic cannabinoids) can remodel the adolescent brain and make it respond differently to more addictive substances, such as cocaine. In the present study, we demonstrate that a history of synthetic cannabinoid exposure in adolescent animals results in distinct molecular and epigenetic changes following initial exposure to cocaine."

In addition to affecting the endocannabinoid system and (potentially) the glutamatergic system, the study found that early cannabinoid use seems to cause epigenetic changes in the prefrontal cortex. This area of the brain controls executive functions like long-term planning and self-control.

"Our findings suggest that exposure to psychoactive cannabinoids during adolescence primes the animals' prefrontal cortex, so that it responds differently to cocaine compared to animals who had been given cocaine without having previously experienced cannabis," study co-senior author Philippe Melas told Science Daily.

One consequence of priming the prefrontal cortex in this way seems to be that cocaine becomes more enjoyable.

"This study suggests that teenagers who use cannabis may have a favorable initial reaction to cocaine, which will increase their likelihood of engaging in its repeated use so that they eventually become addicted, especially if they carry additional environmental or genetic vulnerabilities," Kandel told Science Daily.

Limitations

The researchers noted several limitations in their study, including:

  1. The use of experimenter-administered drug regimens instead of self-administration procedures
  2. The use of synthetic cannabinoids instead of Δ9-THC
  3. The assessment of neurobiological changes in bulk tissue instead of cell type-specific analyses
  4. The lack of in vivo causality experiments rendering the molecular data correlational in nature

They also noted that someone won't necessarily develop an addiction if they happen to have a good first experience with a drug. Still, they suggested that research like this can help to develop better treatments for substance abuse disorders.

"These and other experiments are key to understanding the molecular changes to the brain that occur during drug use," said Dr. Eric Kandel, who is also University Professor and Kavli Professor of Brain Science at Columbia. "This knowledge will be crucial for developing effective treatments that curb addiction by targeting the disease's underlying mechanisms."

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A close up of Bathynomus raksasa

SJADE 2018
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Volcanoes to power bitcoin mining in El Salvador

The first nation to make bitcoin legal tender will use geothermal energy to mine it.

Credit: Aaron Thomas via Unsplash
Technology & Innovation

This article was originally published on our sister site, Freethink.

In June 2021, El Salvador became the first nation in the world to make bitcoin legal tender. Soon after, President Nayib Bukele instructed a state-owned power company to provide bitcoin mining facilities with cheap, clean energy — harnessed from the country's volcanoes.

The challenge: Bitcoin is a cryptocurrency, a digital form of money and a payment system. Crypto has several advantages over physical dollars and cents — it's incredibly difficult to counterfeit, and transactions are more secure — but it also has a major downside.

Crypto transactions are recorded and new coins are added into circulation through a process called mining.

Crypto mining involves computers solving incredibly difficult mathematical puzzles. It is also incredibly energy-intensive — Cambridge University researchers estimate that bitcoin mining alone consumes more electricity every year than Argentina.

Most of that electricity is generated by carbon-emitting fossil fuels. As it stands, bitcoin mining produces an estimated 36.95 megatons of CO2 annually.

A world first: On June 9, El Salvador became the first nation to make bitcoin legal tender, meaning businesses have to accept it as payment and citizens can use it to pay taxes.

Less than a day later, Bukele tweeted that he'd instructed a state-owned geothermal electric company to put together a plan to provide bitcoin mining facilities with "very cheap, 100% clean, 100% renewable, 0 emissions energy."

Geothermal electricity is produced by capturing heat from the Earth itself. In El Salvador, that heat comes from volcanoes, and an estimated two-thirds of their energy potential is currently untapped.

Why it matters: El Salvador's decision to make bitcoin legal tender could be a win for both the crypto and the nation itself.

"(W)hat it does for bitcoin is further legitimizes its status as a potential reserve asset for sovereign and super sovereign entities," Greg King, CEO of crypto asset management firm Osprey Funds, told CBS News of the legislation.

Meanwhile, El Salvador is one of the poorest nations in North America, and bitcoin miners — the people who own and operate the computers doing the mining — receive bitcoins as a reward for their efforts.

"This is going to evolve fast!"
NAYIB BUKELE

If El Salvador begins operating bitcoin mining facilities powered by clean, cheap geothermal energy, it could become a global hub for mining — and receive a much-needed economic boost in the process.

The next steps: It remains to be seen whether Salvadorans will fully embrace bitcoin — which is notoriously volatile — or continue business-as-usual with the nation's other legal tender, the U.S. dollar.

Only time will tell if Bukele's plan for volcano-powered bitcoin mining facilities comes to fruition, too — but based on the speed of things so far, we won't have to wait long to find out.

Less than three hours after tweeting about the idea, Bukele followed up with another tweet claiming that the nation's geothermal energy company had already dug a new well and was designing a "mining hub" around it.

"This is going to evolve fast!" the president promised.

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How were mRNA vaccines developed? Pfizer's Dr Bill Gruber explains the science behind this record-breaking achievement and how it was developed without compromising safety.

How Pfizer and BioNTech made history with their vaccine
Sponsored by Pfizer
  • Wondering how Pfizer and partner BioNTech developed a COVID-19 vaccine in record time without compromising safety? Dr Bill Gruber, SVP of Pfizer Vaccine Clinical Research and Development, explains the process from start to finish.
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  • The Pfizer-BioNTech COVID-19 Vaccine has not been approved or licensed by the Food and Drug Administration (FDA), but has been authorized for emergency use by FDA under an Emergency Use Authorization (EUA) to prevent COVID-19 for use in individuals 12 years of age and older. The emergency use of this product is only authorized for the duration of the emergency declaration unless ended sooner. See Fact Sheet: cvdvaccine-us.com/recipients.

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