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CBD, or cannabidiol, is one of the primary active compounds found in the cannabis plant. Like other cannabis strains, CBD also contains terpenes that contribute to its unique aroma and potential therapeutic effects. Here are some of the most common terpenes found in CBD: Myrcene: Myrcene is one of the most abundant terpenes found in cannabis, inclu...

Think of your brain as an ocean, an ecosystem inhabited by numerous species of fish-like neurotransmitters and their receptors, with currents of electricity connecting and delicately balancing all the different components. Inflammation is like a bloom of red algae, harming everything around it and upsetting the homeostasis of the environment.

Enter our hero, Palmitoylethanolamide (PEA) – a lipid messenger kindred to the endocannabinoid system and a close cousin of anandamide (AEA), the famous endocannabinoid neurotransmitter. Sometimes referred to as “the endogenous version of CBD,” PEA is a powerhouse against inflammation and pain. Like CBD, PEA increases the levels of endocannabinoids and strengthens the endocannabinoid system. And, again like CBD, a constant theme in the scientific literature about PEA is its incredibly strong safety profile.

In our neural ocean metaphor, PEA weighs in as the “most venerable of the leviathans,” the grinning Right Whale, a stalwart fighter in our constant battle against inflammation and pain.

A Mystery

The PEA story begins with a mystery, which leads to another mystery — and ends with the next great wave of the cannabinoid revolution.

We begin during World War 2 – and indeed, geopolitics plays a significant role in our tale. Because of the war effort, we find it a prosperous time for the new-ish field known as “public health.” A healthy population of workers was essential to support the production of war materiel. Two NYC doctors named Coburn and Moore found that if they gave dried eggs to the poor children of the tenements, this helped to prevent rheumatic fever and other ills related to poor nutrition. They also discovered that egg yolks are an anti-inflammatory food.

What makes cannabis cannabis? The aroma of flower and the physiological effects of consuming it come down largely to two things: cannabinoid ratios and terpene content. These twin factors go a long way toward shaping the user experience of a given product, and distinguishing it from myriad other options. But what is the source of these distinctions, whether sweeping or subtle? New research points to the importance of an oft-overlooked influence: cultivation.

Variations in terpene and cannabinoid profiles are typically chalked up to genetics. Individual cultivars, defined by parental inheritance, may be grouped into broad categories according to their genetic predisposition toward a particular dominant terpene — caryophyllene and limonene for “dessert” strains, ocimene for tropical/floral strains, and terpinolene for Jack/haze strains, to name a few — or cannabinoid profile — high-THC, high-CBD, or balanced THC-CBD.

While helpful, these cultivar/genetics-based classification systems obscure an important consideration: the conditions under which the actual plant is grown. To wit, a new study in the journal Molecules finds that clones with identical genetics can produce meaningfully different levels of both types of chemicals when grown “naturally” versus “artificially.” Other recent papers report similar findings under different lights at indoor grows.

Science now confirms what cannabis connoisseurs have argued for years as cultivation has become increasingly commercialized in legal markets: it’s not all nature; nurture matters, too.

A Cultivation Experiment

Published in January 2023, the Molecules1 study was performed by researchers at New York’s Columbia University along with the owners of three independent Northern California cannabis companies: John Casali of Humboldt’s Huckleberry Hill Farms; Tina Gordon of Humboldt’s Moon Made Farms; and Christine Skibola of Novato’s Cosmic View.

Small producers have long been wary of the cannabis industry coming under domination by multistate operators (MSO’s) with the worst practices of corporate America. But the revelations of Russian oligarch money in the coffers of leading MSO Curaleaf appear to vindicate even the most cynical observers. These follow a slew of controversies concerning product safety and labor rights at the company.

Now based in the Boston suburb of Wakefield, adult-use cannabis colossus Curaleaf seems to exemplify the industry’s trajectory — from its origins as a local operation for medicinal users to its current status as a globe-spanning titan generating unsavory headlines and a string of scandals.

The World’s Largest Cannabis Company

Today Curaleaf ranks as the largest cannabis company in the world. Last year, it claimed $1.2 billion in profits. Until recently it had operations in 23 US states with 147 dispensaries, 22 cultivation sites, and 30 processing facilities.

Like other big MSOs, Curaleaf has achieved a dominant position in the cannabis industry by setting up operations primarily in “limited-license states . . . with natural high barriers to entry and limited market participants,” a strategy that helps “to ensure the company’s market share is protected,” according to the company’s annual investor filing in 2020.

But these “high barriers to entry” are hardly “natural.” They are constructed and promoted by policy-makers, regulators, and some opportunistic legalization advocates who favor restricting access to lucrative cannabis business licenses to a small number of well-heeled applicants.

Anyone who has paid any attention to the cannabis “wellness” industry in recent years — whether through state medical and recreational programs or the free-for-all national CBD market — will be familiar with cannabinoid-infused topicals marketed to treat minor aches and pains. Because they’re easy to use and non-intoxicating, these products may serve as familiar, low-risk entry-points for elderly, wary, or cannabis-naive individuals into the wider world of cannabis products.

Cannabis-infused salves, lotions, and the like work because cannabinoid receptors CB1 and CB2 — as well as secondary targets including TRP (“trip”) channels, PPARs (nucleus receptors), and serotonin receptors — are abundantly expressed in skin cells.1,2 Topically applied cannabinoids can bind directly with these receptors and thus reduce local inflammation and pain.

But properly formulated cannabis topicals may be able to do more than just that. For decades, researchers have studied cannabinoids’ ability to treat clinical skin conditions like acne, ulcers, and dermatitis. In the skin, as elsewhere, the endocannabinoid system works broadly to maintain balance, proper functioning, and immune response, including through the synthesis of the endocannabinoids anandamide and 2-AG.3 It’s even possible that cannabinoids taken internally, and not simply via a localized topical, may be able to help — especially if a condition is more widespread.

While skin disease remains a relatively little-known indication for cannabis use, and certainly demands more specialized attention than your standard soothing balm, numerous recent papers suggest it’s an area well worth exploring.

Cannabinoids for Inflammatory Skin Diseases

To start, consider a recent article in the journal Pharmaceuticals4 that examines previous research into cannabis-based medicines for inflammatory skin diseases such as acne,5 eczema, dermatitis, and psoriasis. The Portugal-based authors review 29 studies published between 2003 and 2021, 13 of which used human subjects and the rest cell and animal models. None of the human studies involved oral intake of cannabinoids per se, though one did find that increased consumption of hemp seed oil, but not olive oil, was associated with reduced symptoms of atopic dermatitis. The authors of the original study attributed this to the high concentration in hemp seed oil of polyunsaturated fatty acids, which are endocannabinoid precursors.

On Jan. 26, the FDA issued a CBD policy statement that reaffirmed its longstanding unwillingness or inability to regulate nonpharmaceutical CBD products. The announcement is riddled with disingenuous doublespeak, starting with the wordy title: “FDA Concludes that Existing Regulatory Frameworks for Foods and Supplements are Not Appropriate for Cannabidiol, Will Work with Congress on a New Way Forward.”

After stonewalling for years, the Foot Dragging Administration is basically admitting that its bureaucracy is unable to scale with the scope and magnitude of popular interest in CBD. So it’s passing the buck to Congress.

Perhaps a more incisive title would be: “FDA Concludes that Existing Regulatory Frameworks for Foods and Supplements are Not Appropriate.”

As per usual, the FDA reflexively privileges pharmaceutical CBD, which is so safe it’s not even considered a controlled substance. But as for nonpharmaceutical CBD — the FDA insists it’s too risky for public consumption.

It’s worth noting that cannabidiol (CBD), as a whole plant option or derivative has been available since 2010, and millions of people have used CBD products without apparent harm. A 2018 report by the World Health Organization concluded that CBD “is generally well-tolerated with a good safety profile [and] exhibits no effects indicative of any abuse or dependence potential.” A clinical trial by ValidCare assessing CBD’s impact on human liver function has given the compound a clean bill of health.

Heart disease is the leading cause of death globally. Millions of people treat heart disease by taking statins to regulate their cholesterol. Unfortunately, these drugs can cause muscle weakness and myopathy in some patients. Doctors once thought muscular pain was psychosomatic, but there’s more to it. Statin medications deplete cannabinoid receptor function, according to a recent study by a team of distinguished Italian scientists.

The study, released as a preprint on Research Square before peer review, suggests that simvastatin, a widely used medication, affects enzymes in the endocannabinoidome, the expanded endocannabinoid system encompassing several endogenous fatty acid compounds in addition to anandamide and 2-AG (the two most prominent endocannabinoids). More troublesome, though, is that simvastatin alters genes involved in regulating cannabinoid receptors.

Mapping cannabimimetic pathways manipulated by statins and redesigning existing medications to respect the endocannabinoidome could lead to therapeutic adjuvants that may limit adverse reactions to statins. This is critical, considering that statins are the most prescribed lipid-lowering agents worldwide — not only to lower cholesterol but also to inhibit inflammation and stabilize atherosclerotic plaques.

Statins & Lipid-Lowering Drugs

Statins reduce cholesterol by inhibiting an enzyme in the liver called HMG-CoA reductase. Overall, they lower low-density lipoprotein (bad cholesterol) and triglycerides, while increasing good cholesterol levels.

Lipid regulation helps reduce the risk of cardiovascular disease. The lipidome, however, consists of endocannabinoids and endocannabinoid-like neurotransmitters. And this could be why statin medications, such as simvastatin, while generally well tolerated, can cause serious side effects, including pain and toxic myopathies, in some people.

Could two rights make a wrong? Cannabis and immunotherapy have both gained traction in the oncology field in recent years — one to help treat symptoms and the other as a gentler alternative to chemotherapy — but there’s been some concern that for cancer patients using both, the former could interfere with the latter.1,2  A newly published study in the European Journal of Cancer,3  however, suggests there may be nothing to fear.

Drugs called immune checkpoint inhibitors are a form of immunotherapy that have transformed — with better targeting and less severe side effects — the treatment of many cancers, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors are routinely administered as first-line treatments for NSCLC, either alone or in combination with chemotherapy.

Cannabis, too, has become more widely used among cancer patients over the past decade, paralleling its growing societal acceptance and expanding medical use. In addition to preclinical research and anecdotal accounts indicating that cannabinoids may have anti-cancer effects, cannabis is also well known to mitigate many symptoms and side effects of cancer and cancer treatment, including nausea, pain, and suppressed appetite.

Red Flags from Earlier Studies

Worries about the potential incompatibility of these two treatments stem from the fact that the cannabinoid receptor CB2 is predominately expressed by immune cells, and its activation may suppress immune function. Immunotheraperies like immune checkpoint inhibitors depend upon a robust response to do their work. It’s at least plausible, then, that cannabis might interfere with immunotherapy: instead of helping, it may actually hurt.

In fact, that’s exactly what two previous studies from an Israeli research team in 20194  and 20205  have suggested — though, as the authors of the new paper, also based in Israel, argue right off the bat, those earlier findings come with some pretty large caveats. “These studies included patients with various cancers, treatment regimens, and lines of therapy and were given [immune checkpoint inhibitors] at advanced line shortly before death,” the authors write. “Under these circumstances, the use of cannabis is often a mere surrogate for high-burden symptomatic disease.”

Today’s review comes by the way of an American company named Sweet Sensi. Sweet Sensi CBD products are something you really should consider learning more about, and even purchasing – should you need to re up on your hemp-based items. As with all other reviews, you can expect an honest opinion about all aspects of this business and the products they have for sale.

Most of you know that cannabidiol (CBD) products are a dime a dozen, and for this reason you simply must do some research about what it is you’re looking at. Today’s research revolves around Sweet Sensi CBD.

Sweet Sensi

Sweet Sensi is a CBD brand based out of Austin, Texas. They claim to have the best CBD in Austin, Texas, but I’d argue their lineup is better throughout a much broader region.

Greg Autry is the founder of Sweet Sensi. He’s been dealing with growing hemp, and selling CBD in Austin. You can trace his cultivation of the hemp plant back 25 years. Impressive.

Cannabis contains compounds that directly target cannabinoid receptors. Psychedelics like Lysergic Acid Diethylamide (LSD) target serotonin receptors. By acting through serotonin pathways, LSD affects endocannabinoid synthesis and function, according to a recent study published in the British Journal of Pharmacology.1

The October 2022 BJP study, featuring contributions from Dr. Vincenzo Di Marzo, Gabriella Gobbi, and several other scientists, sought to quantify serotonin and endocannabinoid-like molecules in the brains of mice that were sacrificed after a seven-day LSD regimen. Repeated 30 microgram doses of LSD per kilogram of body weight elicited anxiolytic and prosocial behavior. The researchers from Canada, Italy and Australia also examined how LSD affected the microbiome of the mice after the seven-day, 30-microgram dose routine.

The study noted anti-depressant and anti-anxiety effects triggered by LSD, which altered endocannabinoid tone and affected the serotonin metabolite, kynurenic acid, without impacting the levels of serotonin or its precursor tryptophan. Increased interaction among mice and anxiolytic behavior occurred, in part, through endocannabinoid signaling and corresponded to changes in a few key families of gut bacteria. These results were seen after repeated doses of LSD, not after a single session.

LSD Impacts Endocannabinoid Tone by Binding to Serotonin Receptors

Psilocybin, ayahuasca, mescaline, and LSD cause a psychedelic “trip” by binding to 5HT-2A, a serotonin receptor. This is one of 14 serotonin receptors, which induce a family of enzymes known as phospholipases (PLs). Various serotonin receptors induce different PLs. And two compounds (agonists) that activate the same receptor can promote different enzymes.

Serotonin receptors drive a symphony of endocannabinoid-producing PLs. Previous research has shown that serotonin facilitates the release of 2-AG, a major endocannabinoid, through a phospholipase c (PLC)- dependent mechanism.2 LSD and psilocin (the psychedelic metabolite of psilocybin) induce different PL enzymes by binding to the 5-HT2A receptor.

In recent years, psilocybin and MDMA have been explored as potential treatments for post-traumatic stress disorder, but somewhat more quietly so has cannabis. In fact, according to a few quick searches of PubMed, cannabis has a longer and richer association with PTSD in the scientific literature than any psychedelic. Though you wouldn’t know that by reading the headlines.

Setting aside for a minute how effective psychedelics may or may not be as breakthrough treatments for PTSD, there’s no doubt that cannabis is still much easier for most patients to access.

Recent research – including three new studies (from three different countries) – suggests that growing numbers of PTSD sufferers are medicating with cannabis, and truly finding it helpful.

Depression Drives Cannabis Use

First, a paper in the journal BMC Psychiatry1 from researchers based in Ontario, Canada, provides some insight into cannabis use among PTSD patients during the first wave of the coronavirus pandemic. Between April 3 and June 24 of 2020, 462 individuals with self-reported PTSD completed an online questionnaire that assessed mental health symptoms and cannabis intake both before the pandemic and in the seven days prior to filling out the survey.

Stress, anxiety, and depression worsened across the board, but by categorizing participants according to cannabis use patterns – not using, using less, using the same, or using more – the researchers discovered something interesting. PTSD sufferers who increased their cannabis use during the pandemic were more likely to also experience “meaningful perceived worsening of depression symptoms,” the authors write.