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Pioneering cannabis chemist Dr. Raphael Mechoulam passes away at 92

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Dr. Mechoulam was the first to isolate THC in the 1960s and his research laid the foundation for medical and adult-use weed legalization.


Legendary cannabis researcher and professor Dr. Raphael Mechoulam passed away at 92. The details of his death are not public at this time.

“Raphael Mechoulam was probably the most important and influential cannabis and cannabinoids researcher of the 20th century,” said Leafly’s Nick Jikomes, PhD. “From the initial isolation of THC and CBD from cannabis to the discovery of the endogenous cannabinoids of the body, his contributions to our understanding of cannabinoid biology are second to none,” Jikomes said following the news of Mechoulam’s passing.

photo-of-raphael-mechoulam
Raphael Mechoulam isolated both CBD and delta-9 THC in the earlyt 1960s. (AP photo)

In 1964, Mechoulam published the first research ever that isolated and identified THC as the active compound in cannabis. For the next six decades, Mechoulam helped legitimize and destigmatize cannabis using scientific research. In July 2022, he published a review that charted his life’s work in cannabis.

“After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 years, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids… Δ9-tetrahydrocannabinol and cannabidiol, are approved drugs… For me, intellectual freedom—the ability to do research based on my own scientific interests—has been the most satisfying part of my working life. Looking back, I conclude that I have been lucky, very lucky, both personally and scientifically.”

Dr.  Mechoulam, “A Delightful Trip Along the Pathway of Cannabinoid and Endocannabinoid Chemistry and Pharmacology”

Why Dr. Raphael Mechoulam began studying cannabis

Born in Bulgaria in 1930, Mechoulam escaped the Holocaust and went on to study Biochemistry at The Hebrew University in Jerusalem.

“I was looking for natural products that have not been well evaluated and may possibly be used as drugs or for biological purposes… I was surprised to find out that morphine had been isolated from opium 150 years previously, and cocaine had been isolated from cocoa leaves 100 years previously, the active compound in cannabis had never been isolated in pure form. Some people have worked on that. But the techniques were apparently not good enough. While they knew more or less the active compounds, they never got a pure compound. And so I thought, ‘it’s a good idea to try to look at the chemistry.’”

Dr. Mechoulam

How Dr. Raphael Mechoulam changed cannabis research

Dr. Mechoulam took the first step in a long line of research that has led to legal medical and adult-use cannabis in certain states across the US and a handful of countries around the globe. Dr. Mechoulam started his research by requesting and receiving hashish from local police. “It turned out that we broke the law,” he remembered in a 2021 interview with Live Doctors. “We didn’t know that. And the police broke the law. And we should have ended up in prison.”

Cannabis ready for testing in a lab
(AdobeStock)

He eventually got the OK from the local minister of health and started legally receiving evidence from the police to use for his research.

“At that time I didn’t have a car. I get onto a bus, and people would start looking around, ‘Hey what kind of smell do we have here?’”

Dr. Mechoulam

Dr. Mechoulam and his team injected monkeys with the isolated compounds they found in cannabis and learned that THC was the only active one, since it put the monkeys to sleep. “We published that in 1964,” he said. “(But) there was very little interest in that time.” Mechoulam said he couldn’t get a grant in the US, and was told that, “No Americans used cannabis, only Mexicans.”

How Dr. Mechoulam’s work impacted legalization in the US

DEA-lawsuit-medical-marijuana
A new lawsuit would force the DEA to reconsider the criteria set in 1992 to determine the ‘accepted medical use’ of cannabis. (AdobeStock)

The American government’s interest in cannabis changed a year or two later, when Dr. Mechoulam said a US politician’s son came rushing to him for guidance. They wanted to know if their son’s brain was at risk from smoking pot.

“They came over and at that time we had isolated the first pure batch of THC,” Prof. Mechoulam said. “They took it, they smuggled it into the US. They didn’t have a permit.”

Dr. Mechoulam

According to Dr. Mechoulam, “Some of the research that was done at the beginning in the US was done with the material that we had.” Decades later, US researchers would identify the human body’s endocannabinoid receptors by building on Dr. Mechoulam’s work. Medical and recreational cannabis laws would soon follow, thanks in large part to this trailblazer of cannabis culture.



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autism

Study: Early cannabis use in pregnancy doesn’t predict autism

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Cannabis use during pregnancy has been increasing in the US, and many people may be wondering what impacts this trend could have on children. Some previous research has pointed towards the possibility that prenatal cannabis exposure could increase the likelihood of having autistic children. But a recent study—one of the largest ever conducted on cannabis and autism—found that cannabis exposure in early pregnancy did not lead to higher odds of an autism diagnosis.

What is autism?

Autism is classified as a developmental disorder. It impacts how individuals interact with others, communicate, learn, and experience life. One in 36 Americans are diagnosed with autism; symptoms usually appear during the first two years of a person’s life. Autism is also a spectrum condition—it encompasses a wide variety of different symptoms that an individual might experience, and different levels of health care support may be needed.

Some of the challenges that autistic people might face include having a style of communication that non-autistic people have trouble understanding, having sensory issues because of heightened or reduced sensory perception, and having more repetitive or restricted patterns of behavior than non-autistic peers.

Related

Minnesota OKs Medical Marijuana for Autism, Sleep Apnea

While medical literature classifies autism as a disorder, many autistic advocates point out that many of the “symptoms” of autism are not inherently problematic or disordered; they simply clash with non-autistic expectations, leaving autistic people marginalized. 

Previous research on cannabis exposure and autism

The recent study, conducted by researchers from Kaiser Permanente and UC San Francisco, evaluated whether cannabis use in early pregnancy could increase the likelihood of a woman giving birth to an autistic child. Autism has been linked to a variety of potential environmental causes, but most research points towards genetics as the primary cause.  

One study, published in 2020, did find an association between prenatal cannabis use and autism, leading to questions about whether cannabis use could cause autism. However, otherstudies found no associations. Unfortunately, those studies utilized self-reporting methods, which may have skewed the results due to a potential underreporting of cannabis use. 

Researchers in the recent Kaiser / UCSF used more rigorous methods to determine whether prenatal cannabis use caused higher rates of autism in children.

Studying prenatal cannabis and autism

This recent study was one of the largest ever done on the topic (it included 178,948 pregnancies), but it also utilized a more robust data set for cannabis use and autism.

This recent study was one of the largest ever done on the topic (it included 178,948 pregnancies), but it also utilized a more robust data set for cannabis use and autism. The study incorporated information from Kaiser Permanente Northern California’s integrated health-care system, which universally screens pregnant individuals for cannabis use—via both self-reporting and a urine toxicology test. Kaiser also routinely screens and assesses children for autism.

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The researchers also included related factors in their analysis like sociodemographic data, the additional medications and substances that a mother consumes, and general health conditions.

Prenatal cannabis use not associated with autism

While an initial analysis appeared to indicate an association between autism and prenatal cannabis use, the association disappeared after adjusting for factors like sociodemographic characteristics and the medical conditions of the mother.

This lack of association suggests that mothers who use cannabis during pregnancy are more likely to have autistic children—not because of the cannabis itself, but because of other factors that also increase likelihood of cannabis use. 

While the researchers don’t identify those specific factors, these results shouldn’t be that surprising: For one, Autism has high hereditary rates. Furthermore, cannabis is sometimes used as an effective treatment for symptoms of autism. Separate studies have noted that autistic individuals tend to have lower levels of endocannabinoids in their bodies, which could suggest an impairment of the endocannabinoid system. 

Mothers with autism—or other conditions tied to the same genes as autism—are more likely to both use cannabis and have autistic children; this correlation may help explain the initial results of the study. Still, only more research will offer conclusive answers to these questions. 

Limitations and future research

This study used a strong methodology, with a large and diverse data set. Still, it was limited by the fact that cannabis use was only measured in early pregnancy. Future studies should measure cannabis use throughout pregnancy, and ideally include information like the methods and dosing of the cannabis itself.

While this study suggests prenatal cannabis use is not associated with autism, the authors nonetheless caution that there is evidence that cannabis can impact development in other ways and should be avoided during pregnancy. 



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AMA

Study: Cannabis Shows No Long-Term Impact on Brain Function

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In recent years, the debate surrounding cannabis effect on brain function has intensified, especially as more states and countries move toward legalizing the drug for both medical and recreational use. Historically, marijuana has been associated with cognitive impairments, particularly in areas such as memory, attention, and executive function. However, a new study published by the American Medical Association (AMA) challenges this long-standing view, suggesting that moderate cannabis use does not significantly impair certain cognitive processes such as working memory, reward processing, and inhibitory control. This groundbreaking research shifts the conversation about cannabis, particularly in its medical applications, and prompts a re-evaluation of prior assumptions.

Background: Changing Perceptions of Cannabis

For decades, cannabis was largely viewed as a recreational substance that carried risks of addiction, cognitive decline, and other negative health outcomes, particularly in adolescents and heavy users. Early studies indicated that cannabis use, especially when initiated during adolescence, could impair brain development and lead to long-term cognitive deficits. This perspective influenced policy and public opinion, leading to its classification as a Schedule I substance in the United States, alongside drugs like heroin and LSD.

However, as cannabis legalization has gained momentum, the need for a more nuanced understanding of its effects has become increasingly important. Medical cannabis, in particular, is used to manage conditions such as chronic pain, anxiety, and depression. These evolving applications prompted researchers to take a closer look at how cannabis affects brain function, especially in moderate, controlled doses for medical use.

The AMA Study: Key Findings

The AMA-funded study, published in JAMA Network Open, investigated the long-term effects of marijuana use on cognitive functions. The research focused on adults who were using medical cannabis to manage symptoms like chronic pain, anxiety, and depression. Researchers utilized functional magnetic resonance imaging (fMRI) to assess brain activity related to working memory, reward processing, and inhibitory control tasks at baseline and after one year of moderate cannabis use.

The results were surprising. Contrary to previous assumptions, the study found no significant differences in brain activation between the two time points, even after a year of consistent marijuana use. Specifically, the researchers reported that “working memory, reward, and inhibitory control tasks did not differ statistically from baseline to one year and were not associated with changes in cannabis use frequency.” This suggests that moderate cannabis use for medical purposes does not impair these key areas of cognitive function.

Furthermore, the study noted that prior research on marijuana’s cognitive impacts often focused on adolescents or heavy, recreational users, which could explain the previously observed deficits. The current study’s focus on adults using cannabis for medical purposes, and typically in moderate amounts, paints a different picture, indicating that the cognitive risks associated with cannabis may not apply equally to all users.

Implications for Medical Marijuana Patients

The AMA study offers promising news for medical marijuana patients. Many individuals who use cannabis to manage chronic health conditions often worry about the potential cognitive side effects of long-term use. This research provides some reassurance that moderate use, particularly in adults, may not carry the same risks as previously thought.

For patients dealing with chronic pain, anxiety, or depression, medical marijuana has often been viewed as a trade-off: potential relief from debilitating symptoms in exchange for possible cognitive decline. The findings of this study suggest that for those using cannabis in controlled, moderate amounts, the cognitive risks may be minimal. This is especially important for patients who rely on cannabis to manage their symptoms without the use of more addictive medications, such as opioids.

The Importance of Context: Adolescents vs. Adults

One key takeaway from the AMA study is the distinction between the effects of cannabis on adolescents and adults. Prior studies have shown that cannabis use, particularly when started in adolescence, can lead to long-term cognitive impairments. The adolescent brain is still in a critical stage of development, and cannabis use during this period has been linked to changes in brain structure and function.

However, the AMA study focused on adult users, who have fully developed brains, and the results suggest that moderate cannabis use in this population does not have the same deleterious effects. This highlights the importance of considering age and developmental stage when discussing the risks associated with marijuana use. While cannabis may still pose risks for younger users, adults who use it for medical purposes may experience fewer cognitive side effects than previously believed.

Study Cannabis Shows No Long-Term Impact on Brain Function
Study Cannabis Shows No Long-Term Impact on Brain Function

Long-Term Cognitive Effects: What We Still Don’t Know

While the AMA study provides valuable insights, it also underscores the need for further research. The study focused on light to moderate cannabis use for medical purposes, and it’s unclear whether the findings would hold true for heavier use or for recreational users. Additionally, the study’s participants were adults with chronic health conditions, a group that may respond differently to cannabis than the general population.

Further studies are needed to explore the effects of higher doses of cannabis, different consumption methods (such as smoking vs. edibles), and the long-term cognitive effects across a broader range of populations. As more states legalize cannabis, the number of users is likely to increase, making it even more important to understand the full scope of marijuana’s impact on brain function.

Potential Policy Implications

The AMA’s findings could have significant implications for cannabis policy. As more evidence emerges suggesting that moderate cannabis use does not impair cognitive function, there may be increased pressure to reclassify cannabis under federal law. Currently, its Schedule I classification denotes that it has “no accepted medical use and a high potential for abuse,” a categorization that is increasingly at odds with scientific research and public opinion.

If further research continues to support the AMA’s findings, policymakers may be more inclined to reconsider cannabis’s legal status. Additionally, this research could influence the guidelines and recommendations for medical marijuana use, helping to establish safe, evidence-based dosing protocols for patients.

Conclusion

The AMA study offers new insights into the effects of marijuana on brain function, challenging long-held assumptions about its cognitive risks. For adults using cannabis moderately to manage medical symptoms, the findings are reassuring, suggesting that key cognitive processes like working memory and reward processing are not significantly impacted by long-term use. However, more research is needed to fully understand the broader implications of these findings, particularly in younger populations and heavier users. As the legal landscape around cannabis continues to evolve, studies like this one will be critical in shaping our understanding of marijuana’s role in both medical and recreational contexts.

AMA research is here.



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CBD vs. THC for Anxiety Relief: New Study Finds the Answer

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A groundbreaking study conducted by the University of Colorado Boulder reveals that strains of cannabis high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC) are most effective at alleviating anxiety. This research, the first to examine the acute and extended effects of legal market cannabis products on anxiety symptoms, underscores the therapeutic potential of CBD, offering a safer alternative to THC-dominant strains and prescription medications for anxiety relief.

Cannabis has long been a subject of debate due to its varied effects on different individuals, with some experiencing relaxation and others facing heightened paranoia and anxiety. This study provides scientific backing to the anecdotal evidence, pinpointing CBD as the key compound for anxiety relief without the adverse effects associated with THC.

The research team embarked on a first-of-its-kind experiment involving 300 participants with anxiety, assessing their responses to different strains of cannabis with varying levels of THC and CBD. The study categorized the cannabis strains into three groups: THC-dominant, equal parts THC and CBD, and CBD-dominant, alongside a control group with no cannabis use.

Over the course of four weeks, participants reported their experiences, with those using CBD-dominant strains experiencing significant reductions in tension and anxiety without the impairment or paranoia linked to higher THC levels. Notably, even the THC-containing strains did not exacerbate anxiety over the long term, suggesting that THC’s anti-anxiety effects might still be beneficial compared to abstaining from cannabis use altogether.

This research, published in Cannabis and Cannabinoid Research, offers compelling evidence of CBD’s role in anxiety management, potentially guiding legal prescriptions and product development in countries that have embraced medical cannabis.

Why It Matters: The findings highlight the importance of understanding cannabis’s chemical composition for therapeutic use, particularly for anxiety treatment. By distinguishing the effects of CBD from THC, this study paves the way for safer, more effective anxiety treatments that harness the benefits of cannabis without the risk of exacerbating anxiety symptoms.

Potential Implications: This study could significantly impact the medical cannabis industry, influencing the development of CBD-dominant products for anxiety relief. It may also inform regulatory policies and consumer choices, encouraging a shift towards strains and products that provide the therapeutic benefits of cannabis without the negative side effects associated with high THC levels.

Source: ScienceAlert



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