Author: Vivifi Ventures

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The Entourage Effect in Medicinal Cannabis

The world of medicinal cannabis is vast and intricate, with one term frequently emerging in discussions: the “entourage effect.” But what does it mean, and why is it significant when considering the therapeutic potential of cannabis products?

Understanding the Entourage Effect

Christensen et al. has recently published in Biomedicines a great overview of what we know so far about the entourage effect. Originally coined in a pre-clinical study, the term “entourage effect” referred to the observation where endogenous bio-inactive metabolites enhanced the activity of a bioactive endocannabinoid. In simpler terms, certain inactive compounds, when present, amplified the effects of active ones. This concept was later extrapolated to full-spectrum medicinal cannabis products, suggesting that they might offer a more profound effect than their isolated counterparts.

The entourage effect postulates that the therapeutic impact of the whole plant is greater than the sum of its individual parts. This means that a full-spectrum cannabis product, containing a range of cannabinoids, terpenes, and other compounds, could provide better therapeutic outcomes than a product containing just a single compound, like THC or CBD.

Key Components in Cannabis and Their Interactions

To delve deeper into the entourage effect, it’s essential to understand the primary components of cannabis:

  1. Cannabinoids: These are the most well-known compounds in cannabis, with THC (tetrahydrocannabinol) and CBD (cannabidiol) being the most prominent. While THC is known for its psychoactive effects, CBD is recognized for its therapeutic potential without the “high.”
  2. Terpenes: These aromatic compounds give cannabis its distinctive smell. But beyond aroma, terpenes can also influence the effects of cannabinoids, potentially enhancing their therapeutic properties.
  3. Flavonoids: Present in cannabis, certain flavonoids like cannaflavins have demonstrated therapeutic properties, such as anti-inflammatory effects.

The interactions between these compounds can be classified into two types:

  • Intra-entourage: Interactions between similar compounds, like cannabinoid-to-cannabinoid or terpene-to-terpene.
  • Inter-entourage: Interactions between different types of compounds, such as cannabinoid-to-terpene.

Why the Entourage Effect Matters

The entourage effect is more than just a buzzword. It represents the intricate interplay between various cannabis compounds and their collective therapeutic potential. For instance, while THC is known for its psychoactive properties, its effects can be modulated by the presence of CBD. CBD can influence how THC interacts with certain receptors, thereby altering the overall therapeutic and psychoactive experience.

Terpenes also play a pivotal role in the entourage effect. These aromatic compounds, while primarily known for giving cannabis its distinctive smell, can influence the effects of cannabinoids, potentially enhancing their therapeutic properties. Some terpenes can increase the permeability of the blood-brain barrier, allowing cannabinoids to exert their effects more efficiently. This interaction exemplifies the potential synergistic benefits that can arise when multiple compounds in cannabis work in tandem.

However, while the term often denotes synergistic effects, implying that cannabis compounds target the same receptor system to produce an amplified therapeutic effect, it is essential to recognize that antagonistic interactions might also occur. Such interactions can be as significant as synergistic ones, especially when considering the overall therapeutic profile of a cannabis product.

Furthermore, the term “entourage effect” has been subject to debate within the scientific community. Some critics argue that its usage is primarily for marketing purposes in the cannabis industry, while others believe it holds genuine pharmacological relevance. The term was originally coined to describe bio-inactive compounds potentiating a bioactive compound’s activity. It was later applied to full-spectrum medicinal cannabis products, suggesting an enhanced therapeutic effect compared to isolated compounds.

We can be quite certain that the entourage effect accentuates the intricate and synergistic relationships between the various compounds in cannabis. It suggests that to harness the full therapeutic potential of this plant, one must consider it in its entirety rather than in isolation.

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Cannabis Reclassification: A Step Forward or Regulatory Maneuvering?

In the ongoing theater of state regulation, the Department of Health and Human Services’ (HHS) recent recommendation to reclassify marijuana from Schedule I to Schedule III under the Controlled Substances Act (CSA) has raised eyebrows. Is this change a meaningful stride toward personal freedom, or is it a nuanced adjustment that keeps the core power dynamics intact?

The Controlled Substances Act, found in 21 U.S.C. § 812, has long been a tool for the government to regulate substances, including marijuana. The proposed shift to Schedule III would change the legal standing of cannabis but would not remove the government’s role in its regulation. In essence, the state continues to hold the reins, albeit with a lighter grip. Further, cannabis is not excluded from the CSA like alcohol, “The term [controlled substance] does not include distilled spirits, wine, malt beverages, or tobacco, as those terms are defined or used in subtitle E of the Internal Revenue Code of 1986.” (§ 812(6))

The reclassification would open new regulatory pathways. For example, the federal government could establish a tax system based on THC content, similar to alcohol taxation. The Drug Enforcement Agency (DEA) might also introduce strict licensing requirements, which could disproportionately benefit larger corporations due to the complexities and costs of compliance. Additionally, the government could enact stringent marketing regulations, akin to those for tobacco.

However, the move to Schedule III would ease restrictions on cannabis research, potentially leading to FDA-approved medications. It could also positively impact the SAFE Banking Act by reducing legal risks and providing clearer regulations, thereby potentially attracting more institutional investment. Yet, it’s important to note that these are separate legislative efforts, and the success of one doesn’t guarantee the success of the other.

The HHS recommendation comes in response to President Biden’s call to reevaluate the federal status of marijuana. While some view this as progress, it’s crucial to recognize that Schedule III still subjects marijuana to federal oversight. Most cannabis-related activities would remain federally regulated, leaving the state with significant control over the sector.

The reclassification also doesn’t directly address longstanding issues of racial and class disparities in marijuana law enforcement. For instance, during her time as San Francisco district attorney, Kamala Harris oversaw more than 1,900 marijuana convictions that disproportionately affected minority communities.

President Biden, whose legislative history includes the controversial Violent Crime Control and Law Enforcement Act of 1994, announced a comprehensive pardon for prior federal and D.C. marijuana possession offenses in October 2022. However, the slow implementation of this pardon raises questions about the administration’s commitment to meaningful reform.

While government intervention can distort market dynamics, the proposed reclassification doesn’t fundamentally alter this reality. The state would still have the ability to withhold certain benefits from those with prior marijuana convictions, as the pardons do not include expungements, including the 1,900 convictions overseen by Kamala Harris that disproportionately affected minority communities. This continues to stifle the growth of small and minority-driven cannabis enterprises.

Based on past regulatory changes, full implementation could be a lengthy process. The reclassification would require a formal rule-making process, including public comment, which could take several months to a year. Subsequent federal and state regulatory adjustments could extend this timeline by another 1-2 years, making a 2- to 5-year timeframe for full implementation plausible.

In summary, while reclassification may appear as a significant leap forward, it’s more of a cautious step that doesn’t fully address the core issues. True progress would require not just rescheduling but descheduling marijuana, allowing for greater individual choice and market autonomy, free from extensive state control. Only such a comprehensive shift could begin to heal the wounds left by years of uneven marijuana criminalization.

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Youngsters are ditching the ethanol for greener pastures

Young adults in the U.S., specifically those aged 18 to 34, are reducing their alcohol intake. New survey results from Gallup show that over the past two decades, the percentage of these young adults who drink has fallen from 72% to 62%. Meanwhile, cannabis consumption is on the rise.

While young adults who do consume alcohol are doing so less frequently, older adults are showing an uptick in their drinking habits. Furthermore, younger drinkers are less inclined to overindulge, with only 22% admitting to occasionally consuming more than they believe they should, down from 28% in previous decades. The average number of alcoholic beverages young adults consumed weekly has also decreased from 5.2 two decades ago to 3.6 now.

The changing drinking habits can be attributed in part to a rise in cannabis consumption. Since 2013, its consumption among young adults has nearly doubled. There has also been a demographic shift over the years, with the younger age group becoming more racially and ethnically diverse. This is pertinent as non-white Americans typically drink less. Moreover, there’s a growing health consciousness among young adults. A notable 52% now consider even moderate drinking harmful, a significant increase from the 34% five years ago.

This creates an obvious opportunity for cannabis companies. As alcohol becomes less popular and marijuana use increases, this young cohort should be the one to target. More importantly, we are possibly entering a world with fewer headaches and liver damages that alcohol causes. We look forward to seeing less ethanol down people’s throats and more natural plants in their system. Here is for a healthier and greener century.

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Book Review: Cannabis: Evolution and Ethnobotany

“Cannabis: Evolution and Ethnobotany” by Robert Clarke and Mark Merlin is an expansive and interdisciplinary exploration of the natural origins and early development of this renowned plant. Delving into its historical significance and the profound impact it has had on human societies, the book provides a comprehensive account of cannabis and its diverse uses.

The authors meticulously examine the various aspects of cannabis, from the durable fiber in its stalks to its oil-rich seeds and the psychoactive and medicinal compounds found in its female flowers. Throughout history, these valuable goods derived from cannabis have played a pivotal role in shaping commercial, medical, ritual, and religious practices across cultures, driving the evolution of the plant itself.

Clarke and Merlin offer insights into the historical usage of cannabis for textiles and its migration over millennia. While some sections may be more detailed than others, the book is replete with valuable findings and intriguing discoveries.

The book also sheds light on why humanity continues to depend on cannabis and adapt it to meet our needs. As public interest in cannabis grows and discussions surrounding its myriad uses become more prevalent, this comprehensive resource provides a valuable understanding of its deep-rooted significance in human life.

The authors explore the natural growing conditions of cannabis, highlighting its affinity for exposed riverbanks, lakesides, and agricultural lands that offer ample sunlight and well-drained, nutritious soil. They also delve into the composition of cannabis, revealing that naturally grown plants possess a balanced ratio of CBD and THC. This balanced distribution, which follows a normal distribution curve, contrasts with contemporary varieties that exhibit significantly higher levels of either CBD or THC.

The book delves into the psychoactive properties of cannabis, explaining that the primary psychoactive compound is THC, specifically in its non-psychoactive form known as THCA. To activate its psychoactive effects, cannabis must be heated through decarboxylation, removing the carboxylic acid side chain. For those interested in understanding how the method of ingestion affects the plant’s effects, the authors provide references to additional sources that explore this topic in detail.

Another treat from the book is a captivating journey through the history of the plant. The authors trace its origins millions of years ago in northern Eurasia, speculating that the migration of cannabis southwards during glaciations led to its diversification into indica and sativa strains. They highlight the role of cannabis in the evolution of human cognitive abilities, positing that the ancient mutation resulting in the CB1 receptor, followed by prolonged exposure to THC, may have contributed to the acceleration of human mental powers.

The book intriguingly suggests that cannabis may have played a pivotal role in the development of human cognition at the dawn of agriculture. Carl Sagan’s theorized that cannabis was the only cultivated crop of the Pygmies, suggesting that its use may have influenced the development of our cannabinoid receptors. The authors also present the possibility that early humans first gathered cannabis seeds and later discovered the psychotropic effects by scraping resin from their fingers with their teeth.

In exploring recent history, the authors tell of travelers to India in the 1800s that using cannabis (bhang) had no severe consequences compared to the potential death penalty for drinking liquor. They also touch upon the contemporary (at the time of writing in 2016) state of cannabis cultivation, highlighting the limited number of farmers consciously improving their crops through selection and breeding.

Overall, “Cannabis: Evolution and Ethnobotany” is an insightful and informative book that serves as an excellent resource for those seeking a deeper understanding of the historical significance and evolution of cannabis. Clarke and Merlin’s thorough research makes this book a valuable addition to the field of cannabis studies. A recommended read for those who want to dig deep into this versatile plant, and a source of reference for anyone wanting to write or speak intelligently on the place of cannabis in human history and society.