Le médecin vous prescrira du CBD maintenant

https://doorlesscarp953.substack.com/p/the-doctor-will-cbd-you-now-part?

Therapeutic properties of hemp (Cannabis sativa) and the entourage effect

Jun 14, 2026

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Any extracts used in the following article are for non-commercial research and educational purposes only and may be subject to copyright from their respective owners.

*“Lithuania, Klaipeda. Mobile sand dunes of the Curonian Spit national park and Baltic sea. Largest mobile sand dune in Europe. 98-km long. 2nd only to The Dune of Pilat, France in height”.* CBD-rich hemp varieties are cultivated in this district.

1.0 Introduction

2.0 Discussion

2.1 The global market for CBD
2.2 The gulf between research interest and approved use on prescription
2.3 CBD: An overview
2.4 CBD: Other therapeutic properties
- Antiviral properties
- Antioxidative and anti-inflammatory properties
- Anticancer properties
- For the treatment of demyelinating diseases
- Cyclooxygenase (COX-2) enzyme inhibition
- Anti-aging properties
- Arthritis
- A systems biology approach, and the use of CBD for the prevention and treatment of kidney disease
- Cardiovascular disease and hypertension: vasodilatory effects
- Cutaneous wound healing
2.5 The entourage effect

3.0 Parting shots

4.0 Disclaimer

5.0 References

1.0 Introduction

By Walther Otto Müller - From Franz Eugen Köhler’s Medizinal-Pflantzen. Published and copyrighted by Gera-Untermhaus, FE Köhler in 1887 (1883–1914). Obtained from http://caliban.mpiz-koeln.mpg.de/~stueber/koehler/ . Originally uploaded to wikipedia by w:User:Chmod007 on 19:57, 14 November 2004. An enhanced version was uploaded to wikipedia by w:User:DarkEvil on 17:39, 14 December 2006, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1739269

Hops - Wikipedia — Hops. File:Humulus Lupulus Hopfendolde-mit-hopfengarten.jpg - Wikimedia Commons

The Cannabaceae family (hemp) includes about 170 species in about 11 genera. Humulus (hops), used to add bitterness to beer, are in this family.

Needing little introduction, the Cannabis genus comprises three widely recognised species: C. sativa, C. indica, and C. ruderalis.

Common names for C. sativa include:

Cannabis (the official botanical and accepted name)
Hemp (an industrial or non-psychoactive variety)
Marijuana (varieties grown for their psychoactive or medicinal properties)
Indian hemp
Weed / Pot
Ganja
Mary Jane

C. indica (“of India”) is rich in psychoactive substances, including tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV).

Its street names include:

Purple
Grapes
Hash (derived from hashish)
Marijuana
Weed

Cannabis fibers — Cannabis fibres Plant Profile: Cannabis - Discover + Share

The focus of this Substack is hemp and its many medicinal properties.

Part 2 will extend discussions, including how to make the cannabidiol (CBD) in raw hemp biologically available through decarboxylation, storage advice, and dosing guidelines.

It is legal to purchase hemp in the UK for personal consumption, provided the psychoactive THC content is less than 1 mg per “container”.1

There is no minimum “container” size specified, but the 1 mg limit applies to the entire retail package. It does present something of a loophole, though.

Other countries limit THC by percentage, rather than quantity, and the legislation changes frequently (1 mg supersedes the UK’s 0.2% shown here, from May 2023):

ebot_decarlo_weaver_keeping_the_high_out_of_hemp.pdf

2.0 Discussion

Emphasis is mine in bold, and some passages are lightly reformatted for legibility.

2.1 The global market for CBD

The market for CBD is huge. The global cannabidiol market size was estimated at $18.20 bn in 2025, and is expected to reach $39.74 bn by 2033, with a Compound Annual Growth Rate (CAGR) of 9.9%.

North America dominates the market, with a revenue share of 66.5% and accounting for 80.3% of total revenue.
Hemp-derived CBD held the largest revenue share, at 53.0% in 2025.
Europe is the fastest-growing market.
E-commerce platforms and wider retail availability are helping to drive this growth.2

Cannabidiol market size and growth forecast (2023-2033) — Cannabidiol Market Size And Share | Industry Report, 2033

2.2 The gulf between research interest and approved use on prescription

A PubMed search for the keyword “cannabidiol” returns nearly 9000 papers, and 7276 of these were published in the last 10 years alone:

Yet despite a wealth of experimental data investigating mechanisms and confirming therapeutic properties, at the time of writing, CBD is only approved for prescription by the FDA for just one purpose - to inhibit epileptic seizures.

The prescription oral solution is sold as “Epidiolex”, and it is exclusively approved to treat seizures associated with three specific rare and severe forms of epilepsy.

This is what the FDA has to say about CBD:

Cannabis is a plant of the Cannabaceae family and contains more than eighty biologically active chemical compounds. The most commonly known compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the component that produces the “high” associated with marijuana use. Much interest has been seen around CBD and its potential related to health benefits.
Marijuana is different from CBD. CBD is a single compound in the cannabis plant, and marijuana is a type of cannabis plant or plant material that contains many naturally occurring compounds, including CBD and THC.
The FDA has approved only one CBD product, a prescription drug product to treat seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older.
It is currently illegal to market CBD by adding it to a food or labeling it as a dietary supplement.
The FDA has seen only limited data about CBD safety and these data point to real risks that need to be considered before taking CBD for any reason.
Some CBD products are being marketed with unproven medical claims and are of unknown quality.
The FDA will continue to update the public as it learns more about CBD.
More: https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis

Since when did the corrupt FDA give a hoot about safety data or efficacy?

We last saw such a farcical example of regulatory capture by Big Pharma with DMSO:

Therapeutics/Allopathics

Just Say DMSO

26 avril 2025

Reading time:

Read full story

BTW, this was my most-read Substack post of all time, with over 11,600 views to date.

2.3 CBD: An overview

Cannabis sativa L. (2n ¼ 20) is a well-known plant that has been around since the beginning of time (Small, 2017). This annual plant is a member of the family Cannabaceae and a widespread plant found in varied environments (Andre et al., 2016).

It has been used by humans for over 5,000 years and is one of the oldest plant sources of food and fiber (Appendino et al., 2008). The botanical types of Cannabis sativa differ in terms of their chemical content, plant growth habits, agronomic requirements, and processing (Datwyler and Weiblen, 2006).

Cannabis flowers and leaves have a distinctive aroma, and the plant’s extracts include a variety of beneficial flavonoids, terpenes, and other compounds that are efficient insecticides, fungicides, and therapeutic agents (Pellati et al., 2018).

The flower, leaves, oil, and trichome of the plant have been shown to be cytotoxic, antimicrobial, antioxidant, antihypertensive, antipyretic, and appetite-stimulating (Russo and Marcu, 2017).

The flower extracts with antioxidant activity have been shown to have health-promoting and anti-aging properties, and are utilized to treat a variety of metabolic and chronic disorders, including glaucoma, pain, depression, cancer, liver disease, cardiovascular diseases, inflammation, and metabolic syndrome (Nallathambi et al., 2017).

From: “Cannabis: a multifaceted plant with endless potentials” (2023)

https://pmc.ncbi.nlm.nih.gov/articles/PMC10308385/

Hemp use is as old as civilisation. According to archaeological finds, it’s been in use since at least 8000 BC.

Its medicinal properties were first documented by the legendary Chinese Emperor Shen Nung around 2737 BCE. He prescribed topical hemp oils and teas for pain relief, according to the Pen-Ts'ao Ching materia medica book.3

Contrast this to the FDA, which couldn’t recognise a useful natural medicinal product if it tripped over it on a dark night.

Our first paper provides a great introduction to CBD.

Key takeaways from “An Overview of Cannabidiol” by Sideris et al. (2024):4

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients.
Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019.
CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a “high.”

Cannabidiol (CBD) was isolated from Minnesota hemp in the 1940s by Adams et al,¹ and its lack of intoxicating properties was first noted in 1946.² The first indication of its biological activity was identified through its ability to prolong sleep induced by a barbiturate in an animal model.³ Through the advent and refinement of chromatography techniques, CBD was reisolated and its structure elucidated by Mechoulam et al⁴ at the Hebrew University >20 years later in 1963.

As the PubMed publishing profile shows, it took until the 1970s before we knew the biological role of CBD:

It was not until experiments in the 1970s that CBD’s important biological role was identified in the context of its ability to interact with other major cannabinoids such as delta-9-tetrahydrocannabinol (THC). Extracts of cannabis with varying concentrations of CBD and THC produced markedly different behavioral effects, and CBD mitigated THC’s anxiogenic and cardiovascular effects in healthy volunteers.⁵ Additional evidence emerged of its independent benefits for seizures,⁶ and to this day, there is great interest in CBD’s therapeutic potential.

It’s highly soluble in fats (lipophilic), but not in water:

CBD is a nonintoxicating cannabinoid with a complex pharmacological profile. It is highly lipophilic, rapidly distributing from the blood to the brain, adipose tissues, and other organs.⁷ It can be consumed via inhalation, oral, intravenous, or transdermal routes, either as a purified isolate extracted from cannabis or hemp (cannabis with <0.3% THC) or as part of a cannabis extract with other phytocannabinoids and chemicals.⁸

The half-life of CBD is from 24-31 hours; it can remain biologically active for several days:

Human pharmacokinetic data show modest bioavailability, quick maximal concentration, and long half-life of CBD ranging from 24 hours via intravenous route to 31 hours postinhalation.⁷^,⁹ Repeated oral administration of CBD can have an elimination half-life of up to 5 days; time to maximum concentration has ranged from approximately 1 to 5 hours.^10–12

Some of us are genetically deficient in the Cytochrome P450 (CYP450) enzyme superfamily. This means that bioavailability is higher, and the effective dose is lower, with a greater risk of overdose or side effects.

There is also a feedback process, as CBD is a potent inhibitor of some CYP450 enzymes.

Fortunately, CBD is relatively safe, in comparison to other drugs:

Pharmacokinetics and pharmacodynamics are variable, depending on context and route of administration.⁷^,^9–11^,^13–17 CBD is metabolized by cytochrome P450 into 3 main metabolites: 7-hydroxy-CBD, 7-carboxy-CBD, and 6-hydroxy-CBD, which may have their own distinct activities.⁷^,⁸
It is relatively safe, with oral doses of up to 1600 mg being well-tolerated, but common side effects include diarrhea, sedation, decreased appetite, and elevated liver enzymes with repeated, high doses.¹²^,¹⁸ More studies are needed to identify drug-drug interactions, long-term side effects, and teratogenicity.¹⁹^,²⁰ Many of these side effects could be attributable to other medications administered concomitantly,²¹ as there are known and predicted drug-drug interactions.²² CBD is a potent inhibitor of hepatic cytochrome P450 enzymes, including CYP2C19 and CYP3A4.²³

CBD has a range of molecular targets:

Figure 1.:
Diverse molecular targets of CBD. CBD’s molecular targets include G-protein coupled receptors, transient receptor potential, sodium, and calcium channels, as well as enzymes.
In addition to targeting the eCB system, CBD is an agonist of serotonin 5-HT1a receptors,³⁵ α1³⁶ and α3³⁷ glycine receptors, the ionotropic cannabinoid receptors including chemo- and thermosensitive members of the TRP channel superfamily TRPV1–4, TRPA1,³¹ ^, ³⁸ ^, ³⁹ and an antagonist of the menthol receptor TRPM8.³¹
CBD is also an inverse agonist for 3 other G-protein receptors,⁴⁰ including GPR3, which has been implicated in the development of neuropathic pain.⁴¹ Preclinical studies suggest that CBD is an NAM at the µ and δ opioid receptors,⁴² partial agonist at dopamine D2 receptors,⁴³ and an agonist at the adenosine A1⁴⁴ and A2A receptors.⁴⁵
Moreover, CBD can modulate intracellular calcium levels through direct interactions with mitochondria,⁴⁶ ^, ⁴⁷ blocks voltage-gated T-type calcium channels on murine sensory neurons,⁴⁸ and also activates the PPARγ nuclear receptors with resultant anti-inflammatory effects.⁴⁹ Blockade of the voltage-dependent sodium channels, Na_v1.1-1.7⁵⁰, and more recently, Na_v1.8⁵¹ are additional mechanisms of CBD action.
Interestingly, CBD was more potent at inhibiting repetitive action potentials than the local anesthetic bupivacaine.⁵¹ CBD indicates cannabidiol; eCB, endocannabinoid; GPR3, G-protein coupled receptor 3; PPARγ, peroxisome proliferator-activated receptor gamma; TRP, transient receptor potential channel.

Therapeutic neurobiological indications include seizures, anxiety and depression, and for treating opioid drug addiction:

Earliest studies using CBD in animals provided direct evidence for its potent anticonvulsant effects⁵²^,⁵³ and ability to modulate the effect of other antiepileptic drugs.⁵²^,⁵⁴
The exact mechanism of action of CBD’s anticonvulsant effects has not yet been established, but may involve sodium channels and serotonin receptors.⁵⁵ In 2018, the US Food and Drug Administration (FDA) approved the first cannabis-derived CBD oral solution, Epidiolex, for refractory seizures associated with Lennox-Gastaut and Dravet syndromes.^56–58
Its indication was expanded in 2020 to include seizures associated with tuberous sclerosis complex.⁵⁹ Upon initial approval, the Drug Enforcement Administration classified Epidiolex as Schedule V, but as of 2020, the prescription medication has been descheduled.⁶⁰
Anxiety and Depression
With so many receptor and channel targets and promising preclinical findings, there is interest in CBD’s use for treating psychiatric and neurologic conditions. Owing to its documented modulation of 5-hydroxytryptamine 1A (5-HT1A) serotonin receptors, it is not surprising that preclinical models consistently demonstrate that CBD has anxiolytic properties.^61–66
Rodent models also provide evidence for CBD’s antidepressant-like effects⁶⁷ and attenuation of trauma-related fear memory in models of posttraumatic stress.⁶⁸^,⁶⁹ CBD also reduced compulsive behaviors in rodents,⁷⁰ likely via modulation of the endocannabinoid system.⁷¹
In a study with patients who suffered from social anxiety disorder, a single pretreatment with 600 mg CBD 1 hour before a simulation public speaking test decreased self-reported anxiety and reduced physiological measures of anxiety compared to placebo.⁷²

Addiction
Another potential use of nonintoxicating CBD is its role in cue-induced opioid craving and other addictive behaviors including alcohol and cannabis use disorders.⁷⁴^,⁷⁵
Preclinical findings suggest that CBD may help reduce opioid withdrawal symptoms⁷⁶ and inhibits reinstatement of cue-induced opioid-seeking behaviors in rodents.⁷⁷
In postmortem analysis of rat brains, treatment with CBD normalized changes of CB1 receptor mRNA expression and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate ionotropic receptor subunit 1 (GluR1) in the nucleus accumbens induced by heroin.⁷⁷
CBD also inhibits the reuptake and hydrolysis of AEA, and the resulting increase in endocannabinoid tone may mitigate withdrawal symptoms.⁷⁸ CBD may also affect reward circuitry through non-eCB mechanisms, but more studies are needed to clarify exact mechanisms, which could be different depending on the substance of abuse.

It’s also useful for treating several different types of pain:

ANALGESIC POTENTIAL OF CBD: PRECLINICAL PAIN MODELS
Potential analgesic properties were first evaluated in studies in the 1970s in rodent models of abdominal constriction⁸² and acetic-induced writhing, hot plate, and Randall-Selitto paw pressure tests.⁸²^,⁸³
^…In a recent systematic review and meta-analysis of preclinical studies evaluating cannabinoids and endocannabinoid modulators for antinociceptive effects, the authors identified 17 studies in which over 500 rodents were dosed with CBD after injury or disease onset.⁸⁴
Across a broad range of models and dosing paradigms, CBD decreased pain-like behaviors.⁸⁴ Pretreatment⁸⁵ with CBD relative to an injury may also prevent the development of or significantly attenuate pain-like behaviors. Notably, newer studies suggest that CBD may only produce analgesic effects on established pain or during inflammatory states.^86–88 There are several limitations with these animal studies including the risk of bias and models that cannot fully recapitulate multidimensional clinical pain.⁸⁴
Neuropathic Pain
Neuropathic pain is a debilitating condition that can be caused by diseases such as diabetes, iatrogenic nerve damage, or medical treatments such as chemotherapy.⁸⁹
Rodent models of neuropathic pain attempt to recapitulate symptoms of neuropathy, primarily by inducing mechanical or chemical damage to the sciatic nerve or one of its branches.⁹⁰ Repeated systemic administration of CBD after chronic constriction injury,^91–95 partial sciatic nerve ligation,⁸⁶ sciatic nerve ligation,³⁷ spared-nerve injury,⁹⁶ chemotherapy,⁹⁷^,⁹⁸ or streptozotocin⁹⁹^,¹⁰⁰ reduced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner, without inducing motor impairment, catalepsy, or sedation.
Moreover, CBD can enhance morphine’s antinociceptive effect in established neuropathic pain, while attenuating morphine-induced analgesic tolerance.¹⁰¹

CBD is particularly useful for targeting pain associated with inflammation:

Inflammatory and Acute Postoperative Pain
Painful conditions characterized by significant inflammation may be particularly amenable to CBD treatment, with both peripheral and central mechanisms of action at play.
Models of inflammatory pain include injecting animals’ paws (intraplantar) with irritants and chemicals such as carrageenan or complete Freund’s adjuvant (CFA), administering irritants topically to the skin, or directly injecting them into the knee to induce arthritis.¹⁰⁷

CBD also inhibits pro-inflammatory prostaglandin E2 and cyclooxygenase activity:

Oral CBD administered 2 hours after carrageenan-induced paw inflammation in rats reduces thermal hyperalgesia at low, but not higher doses.⁸⁸ Repeated CBD administration dose-dependently reduced edema and decreased levels of the proinflammatory prostaglandin E2 and cyclooxygenase activity in this model, supporting a potent anti-inflammatory effect. Reduction of thermal hyperalgesia by CBD in carrageenan-induced pain may also involve the TRPV1 channel.⁹¹
^…Topically applied CBD reduced edema, local and systemic inflammatory marker, myeloperoxidase, and tumor necrosis factor alpha (TNF-α), respectively, in an inflammatory model.¹⁰⁸ Moreover, a single topical administration or systemic injection of CBD decreased acute inflammation from systemic administration of lipopolysaccharide.¹⁰⁸

For arthritis:

CBD also ameliorated symptoms of spontaneous or induced models of arthritis. In a canine model of spontaneous osteoarthritis (OA) where both veterinarian and owner independently rated their dog’s behaviors without knowledge of treatment allocation, CBD decreased pain scores, eased walking and running, and facilitated standing from a sitting or lying-down position.¹⁰⁸
Intra-articular injection of CBD after arthritis induction in a rodent model decreased joint afferent firing, reduced mechanical allodynia, and attenuated leukocyte rolling and joint hyperemia, surrogates of inflammatory processes.¹⁰⁹
Prophylactic CBD administrations also prevented the development of mechanical allodynia and nerve demyelination.¹⁰⁹ Systemic CBD at the first signs of collagen-induced arthritis likewise decreased inflammation assessed by its ability to suppress spontaneous TNF release from arthritic synovial cells.¹¹⁰
In a model of incisional pain, which is largely utilized to study acute postoperative pain, injection of CBD systemically or into the rostral anterior cingulate cortex of the rat brain reduced mechanical allodynia.
Lower CBD doses produced conditional place preference (CPP) without affecting incision pain evoked by mechanical stimulation of the affected paw. CPP in incised rats given CBD suggests that it reduces pain aversiveness, since CPP could not be elicited in sham animals.¹¹¹ Collectively, this study demonstrated that CBD can target both the nociceptive and affective-motivational dimensions of pain in an acute postoperative rodent pain model.

Its effects aren’t just theoretical or lab-based:

CLINICAL STUDIES EVALUATING CBD FOR PAIN
Many initial clinical studies published on the effect of CBD on pain were conducted using CBD:THC mixtures rather than CBD isolate. While these showed promising effects in neuropathic pain, drop-out rates were high, potentially due to THC’s adverse effects (AEs).^112–114
In a small placebo-controlled, crossover trial of CBD extract via sublingual spray and other cannabis constituents, CBD over 2 weeks reduced pain scores in patients with neurological disorders.¹¹⁵
A case series reported that daily oral CBD (though in a ratio of CBD to THC of 30:1) for 3 weeks was well-tolerated and reduced pain scores in kidney transplant patients with neuropathic and OA pain.¹¹⁶
Given THC’s psychoactive side effects, together with its potential for dependence, clinical trials evaluating the effectiveness of purified or CBD-rich cannabis products for pain are critical. Importantly, CBD itself does not produce a signal for abuse liability in clinical studies.^117–119

FDA or no FDA, 62% of CBD users have self-medicated to treat a medical condition, but such products are often not pharmaceutical grade, and stated active ingredient levels may be incorrect, and contamination can be a problem:

Cross-Sectional Studies of Cannabidiol Users
CBD is widely marketed and available in the United States, and increasing numbers are using it for wellness and to treat a variety of ailments.¹²⁰ In a cross-sectional survey of CBD users, approximately 62% reported using CBD for a medical condition, led by chronic pain and arthritic joint pain.¹²¹
In a survey of patients with fibromyalgia, 60% reported trying it in the past typically because of inadequate relief from other medications; a third of respondents detailed current use primarily for management of pain, anxiety, and to help with sleep.¹²² In a secondary analysis of the current CBD users, the majority substituted CBD for other medications, including opioids (53.1%), nonsteroidal anti-inflammatory drugs, benzodiazepines, or gabapentinoids.¹²³
CBD use is common in patients presenting for orthopedic surgical care.^124–126 In a cross-sectional survey of patients presenting for evaluation with spine surgeons in an urban setting, 25.2% of respondents used CBD, with the majority of those using CBD for back and neck pain.¹²⁴
Of those who used CBD, 46% reported improvements in pain, while 33% and 20% reported improvements in sleep and anxiety, respectively. In a survey of patients who had undergone total hip or knee arthroplasty at a tertiary care, urban orthopedic hospital, 22% reported using CBD at some point during the perioperative period.¹²⁵
In this study, there were no differences in postoperative pain satisfaction between those who used CBD and those who did not. In another survey study of new patients who visited an orthopedic surgery sports medicine clinic, 19% reported using CBD and 30.9% of whom also reported using marijuana, and the pain intensity in the affected joint was significantly higher in CBD users.¹²⁶
It is important to note that the widely available CBD products that consumers and patients are using outside of clinical trials are not pharmaceutical grade, not federally regulated, and relatively low-dose¹²⁷ compared to FDA-approved prescription CBD therapeutic doses.
Consequently, products are often mislabeled, contain intoxicating amounts of THC, and may also contain other contaminants.^128–130 In a 2017 study, CBD and other cannabinoid content were measured in 84 CBD products sold online by 31 companies in the United States.
Approximately 43% of products were under-labeled, 26% were over-labeled, and 31% accurately reflected CBD content. However, THC was unexpectedly detected in approximately 21% of the samples, and at levels that could cause intoxication or impairment.¹²⁸
Moreover, in states with legal medical cannabis programs, quality control and labeling of cannabis products are not ubiquitous requirements.¹³¹ Patients who register in state programs for medical purposes may also face similar issues with lack of regulation leading to unreliable cannabinoid content.
Because good manufacturing practices for CBD products do not exist currently, content and concentration of cannabinoids in ubiquitously available products vary widely, products are oftentimes mislabeled, and results from cross-sectional studies are subject to bias. Findings from these published studies must be interpreted within the context of these limitations.¹²⁸^,¹³²^,¹³³
More: https://journals.lww.com/anesthesia-analgesia/fulltext/2024/01000/an_overview_of_cannabidiol.7.aspx

2.4 CBD: Other therapeutic properties

CBD demonstrates broad-spectrum therapeutic properties. It cannot be patented by itself, as it’s a naturally occurring compound.

It’s no surprise that Big Pharma hates it. I could probably justify a Substack for each of these, and there will be others that I haven’t shortlisted.

Please follow the links for further reading.

Antiviral properties

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response (2021)
… Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription.
CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARSCoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population.
This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7987002/

Antiviral activities of hemp cannabinoids (2023)
Hemp is an understudied source of pharmacologically active compounds and many unique plant secondary metabolites including more than 100 cannabinoids.

Let me take a wild guess on who lobbied for this:

After years of legal restriction, research on hemp has recently demonstrated antiviral activities in silico, in vitro, and in vivo for cannabidiol (CBD), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and several other cannabinoids against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), and γ-herpes viruses.
Mechanisms of action include inhibition of viral cell entry, inhibition of viral proteases, and stimulation of cellular innate immune responses. The anti-inflammatory properties of cannabinoids are also under investigation for mitigating the cytokine storm of COVID-19 and controlling chronic inflammation in people living with HIV.
More: https://portlandpress.com/clinsci/article/137/8/633/232928/Antiviral-activities-of-hemp-cannabinoids

Lobbyists were successful at outlawing hemp production and research when they managed to coerce the US government into passing the Marihuana Tax Act of 1937.

Lobbyists included the powerful newspaper magnate William Randolph Hearst (who owned extensive timber operations and wood-pulp paper mills) and the DuPont chemical company (which had patented nylon in 1935), which viewed hemp as an economic threat to their paper and synthetic fibre industries.

The alcohol and tobacco industries also had a vested interest in eliminating the competition.

It was a similar story in the UK when cannabis and hemp were restricted in 1928 by the Dangerous Drugs Act.5 6 7 8

Antioxidative and anti-inflammatory properties

Antioxidative and Anti-Inflammatory Properties of Cannabidiol (2019)
CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied.
In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress.
Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.
… CBD is a terpenophenol compound containing twenty-one carbon atoms, with the formula C₂₁H₃₀O₂ and a molecular weight of 314.464 g/mol (Figure 1). The chemical structure of cannabidiol, 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol, was determined in 1963 [13].
The current IUPAC preferred terminology is 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol.
Naturally occurring CBD has a (−)-CBD structure [14]. The CBD molecule contains a cyclohexene ring (A), a phenolic ring (B) and a pentyl side chain. In addition, the terpenic ring (A) and the aromatic ring (B) are located in planes that are almost perpendicular to each other [15]. There are four known CBD side chain homologs, which are methyl, n-propyl, n-butyl, and n-pentyl [16]. All known CBD forms (Table 1) have absolute trans configuration in positions 1R and 6R [16].
Figure 1.
Chemical structure of cannabidiol (CBD)

Figure 2.
Direct antioxidant effects of CBD (closed arrows indicate reducing effects; opened arrows indicate inducing action).
Figure 3.
Indirect antioxidant and anti-inflammatory effects of CBD (closed arrows indicate inhibition; opened arrows indicate activation.
CBD reduces oxidative conditions by preventing the formation of superoxide radicals, which are mainly generated by xanthine oxidase (XO) and NADPH oxidase (NOX1 and NOX4). This activity was shown in the renal nephropathy model using cisplatin-treated mice (C57BL/6J) [23] and in human coronary endothelial cells (HCAEC) [24]. In addition, CBD promoted a reduction in NO levels in the liver of doxorubicin-treated mice [25] and in the paw tissue of Wistar rats in a chronic inflammation model [26].
CBD also reduces reactive oxygen species (ROS) production by chelating transition metal ions involved in the Fenton reaction to form extremely reactive hydroxyl radicals [27]. It was shown that CBD, acting similarly to the classic antioxidant butylated hydroxytoluene (BHT), prevents dihydrorodamine oxidation in the Fenton reaction [28]. In addition, CBD has been found to decrease β-amyloid formation in neurons by reducing the concentration of transition metal ions [29].
In addition to the direct reduction of oxidant levels, CBD also modifies the redox balance by changing the level and activity of antioxidants [19,26]. CBD antioxidant activity begins at the level of protein transcription by activating the redox-sensitive transcription factor referred to as the nuclear erythroid 2-related factor (Nrf2) [30], which is responsible for the transcription of cytoprotective genes, including antioxidant genes [31].
CBD was found to increase the mRNA level of superoxide dismutase (SOD) and the enzymatic activity of Cu, Zn- and Mn-SOD, which are responsible for the metabolism of superoxide radicals in the mouse model of diabetic cardiomyopathy type I and in human cardiomyocytes treated with 3-nitropropionic acid or streptozotocin [32].
Repeated doses of CBD in inflammatory conditions were found to increase the activity of glutathione peroxidase and reductase, resulting in a decrease in malonaldehyde (MDA) levels, which were six times higher in untreated controls [26].

Figure 4.
Major effects of CBD on several membrane receptors (AEA, anandamide; 2-AG, 2-arachidonoylglycerol; FAAH, fatty acid amide hydrolase; AMT, AEA membrane transporter; ROS, reactive oxygen species; Ub, ubiquitin; p65, transcription factor NF-κB; Nrf2, nuclear factor erythroid 2-related factor 2; ARE, antioxidant response elements.
Blue arrows indicate agonist activity; red arrows indicate antagonist activity; dashed blue arrows indicate weakly agonistic activity; green arrows indicate endocannabinoid agonist activity; grey arrows indicate chemical and biological effects).
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7023045/

Anticancer properties

As well as having its own anti-cancer properties, CBD also acts synergistically with existing treatments to increase their efficacy, and it helps to reduce some of the side effects of treatment.

Research shows inhibitory effects with the following cancer types:

Cervical
Breast
Lung
Pancreatic
Colon
Prostate
Leukaemia
Melanoma

Anti-Cancer and Anti-Proliferative Potential of Cannabidiol: A Cellular and Molecular Perspective (2024)
Abstract
Cannabinoids, the bioactive compounds found in Cannabis sativa, have been used for medicinal purposes for centuries, with early discoveries dating back to the BC era (BCE). However, the increased recreational use of cannabis has led to a negative perception of its medicinal and food applications, resulting in legal restrictions in many regions worldwide.
Recently, cannabinoids, notably Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), have gained renewed interest in the medical field due to their anti-cancer properties. These properties include the inhibition of tumour growth and cell invasion, anti-inflammatory effects, and the induction of autophagy and apoptosis.
As a result, the use of cannabinoids to treat chemotherapy-associated side effects, like nausea, vomiting, and pain, has increased, and there have been suggestions to implement the large-scale use of cannabinoids in cancer therapy.
However, these compounds’ cellular and molecular mechanisms of action still need to be fully understood. This review explores the recent evidence of CBD’s efficacy as an anti-cancer agent, which is of interest due to its non-psychoactive properties.

CBD has multiple modes of action, which makes it harder for a tumour to evade it:

The current review will also provide an understanding of CBD’s common cellular and molecular mechanisms in different cancers. Studies have shown that CBD’s anti-cancer activity can be receptor-dependent (CB1, CB2, TRPV, and PPARs) or receptor-independent and can be induced through molecular mechanisms, such as ceramide biosynthesis, the induction of ER stress, and subsequent autophagy and apoptosis.
It is projected that these molecular mechanisms will form the basis for the therapeutic applications of CBD. Therefore, it is essential to understand these mechanisms for developing and optimizing pre-clinical CBD-based therapies.

Figure 1.
Summary diagram of the proposed benefits of phytocannabinoids. Special attention is given to the anti-cancer and anti-inflammatory capabilities of CBG, CBN, and CBD and their lack of calming or psychoactive effects, which has justified their pursuit in medical research, particularly on CBD over the THC and THC derivatives. * = beneficial effects; *** = negative effects.

Figure 3.
Schematic representation of the anti-cancer mechanisms of CBD. CBD acts as an agonist (activator) for the receptors TRPV1 and Transient Receptor Potential (TRP) channels are integral membrane proteins that act as vital cellular sensors. In biochemistry, their main function is to convert physical and chemical environmental signals into biochemical changes—primarily by altering membrane potential or increasing intracellular calcium (Ca²⁺) concentrations. in most cancers, and with a low, but effective, affinity for the CB receptors (CB₁ and CB₂) to promote the downstream activation of pathways essential for cancer cell autophagy, reduced proliferation, and invasion, as well as apoptosis.
At the same time, acting as an antagonist for GPR55 leads to inhibiting tumour cell growth. The PPARγ-mediated COX-2-BCL2 pathway has been reported mainly in lung cancer.
At the same time, CB receptor- and TRPV1-mediated CBD signalling were demonstrated in breast cancer, prostate cancer, and gliomas, among other types of cancer, which lead to apoptosis/reduced invasion/reduced proliferation and autophagy through varying pathways, such as the ICAM-1, the pAKT inhibition of mTORC, and the induction of cell cycle arrest. ↑ = increase/upregulation; ┴ = inhibition.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC11171526/

Cannabidiol (CBD) as a Promising Anti-Cancer Drug (2020)
Abstract
Simple Summary
The use of cannabinoids containing plant extracts as herbal medicine can be traced back to as early as 500 BC. In recent years, the medical and health-related applications of one of the non-psychotic cannabinoids, cannabidiol or CBD, has garnered tremendous attention. In this review, we will discuss the most recent findings that strongly support the further development of CBD as a promising anti-cancer drug.
Abstract
Recently, cannabinoids, such as cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), have been the subject of intensive research and heavy scrutiny. Cannabinoids encompass a wide array of organic molecules, including those that are physiologically produced in humans, synthesized in laboratories, and extracted primarily from the Cannabis sativa plant.
These organic molecules share similarities in their chemical structures as well as in their protein binding profiles. However, pronounced differences do exist in their mechanisms of action and clinical applications, which will be briefly compared and contrasted in this review. The mechanism of action of CBD and its potential applications in cancer therapy will be the major focus of this review article.
Keywords: cannabinoids, cannabidiol, CBD, anti-cancer drug

Figure 1.
Endocannabinoid system. (A) Chemical structures of two endogenous cannabinoids, 2-arachidonylglycerol (i, 2-AG) and N-arachidonylethanolamine (ii, AEA), and two representative exogenous cannabinoids from Cannabis sativa, cannabidiol (iii, CBD) and Δ⁹-tetrahydrocannabinol (iv, Δ⁹-THC). (B) Schematic diagrams of the signaling transduction pathways of the endocannabinoid system. 2-AG and AEA are agonists of CB₁ and CB₂.
Some of the downstream effects include: (1) upregulation of p42/p44 mitogen-activated protein kinases (MAPKs) by direct inhibition of adenylyl cyclase (AC) and direct activation of phospholipase C (PLC), leading to the induction of neuronal growth, interleukin production, and inflammation. PKA: protein kinase A. PKC: protein kinase C. (2) Activation of p38 MAPK, which induces inflammation and apoptosis. (3) Activation of the phosphatidylinositol-3-kinase (PI3K)/AKT and the mammalian target of rapamycin (mTOR) signaling pathways.
Under certain conditions, these endocannabinoids can also induce transcription, cell survival, proliferation, and differentiation through similar pathways. Additionally, the cannabinoid receptors can also modulate ion channels including G protein-coupled inwardly-rectifying potassium channels (GIRKs) and voltage (V)-gated calcium channels.

Figure 5.
CBD’s effects on cancer cells and infiltrating immune cells. (A) Through its interactions with the CB₁, CB₂, and TRPV1 receptors, CBD induces cell cycle arrest and apoptosis in cancer cells. (B) CBD also binds the CB₁ and CB₂ receptors on the infiltrating inflammatory cells and disrupts the pro-tumorigenic cytokine production, thus leading to ineffective immunosuppression and promoting tumor cell death. ROS production by phagocytic cells disrupts the ER and mitochondrial homeostasis in tumor cells leading to apoptosis. UPR: unfolded protein response.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7693730/

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis (2020)
Abstract
In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings.
Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome.
Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis.

Unsurprisingly, you can only legally use them with cancer treatments, not as a cancer treatment themself:

However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients.
Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.
Keywords: cancer, cannabis, cannabinoid, terpene, flavonoid, cytotoxicity, entourage effect

Some terpenes, such as myrcene, may be carcinogenic because they exhibit cytotoxic effects and decrease DNA damage. But the vast majority of those found in cannabis exhibit antitumour effects:

3. Terpenes
More than 20,000 terpenes appear in nature, from every plant, flower, and even some insects. Relatively few of these compounds–about 200–are found in cannabis. According to recent publications [142,143], 50 cannabis terpenes can be found in North American chemovars, but some are more commonly found (Figure 2).
The monoterpene myrcene as well as the sesquiterpenes β-caryophyllene and α-humulene appear to be present in most cannabis cultivars. Other compounds commonly found include alpha-pinene, limonene, linalool, bisabolol and (E)-β-farnesene while some others, in particular sesquiterpenes, are difficult to identify.
As a result, the reported terpene profiles of cannabis cultivars may present incomplete portraits of the actual terpenes present in the plant [144]. Furthermore, even within a plant, the localization of the sample taken may also alter the terpene profile.
Stereochemistry is also not consistently described in cannabis cultivars. These issues make it difficult to fully understand the diversity of terpenes in cannabis and complicates the analysis of studies using extracts or botanical preparations [143].
Generally, terpenes are typically found in cannabis flowers at levels of 2–5%, but can have much higher concentrations in various products (vaping oils, for example). Yet, information about many of the terpenes is available in regard to their potential beneficial effects. Some of those effects, related to cancer, are described below and in Table 2.
Figure 2.
Structure of various terpenes found in the Cannabis plant.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7409346/

With breast cancer, researchers found that CBD induces an interplay among PPARγ (gene activation), mTOR (a kinase that can act as a switch for cell growth) and cyclin D1 (a critical regulatory protein that drives cell cycle progression) in favour of apoptosis (cancer cell programmed cell death):

Novel mechanism of cannabidiol-induced apoptosis in breast cancer cell lines (2018)
Abstract
Studies have emphasized an antineoplastic effect of the non-psychoactive, phyto-cannabinoid, Cannabidiol (CBD). However, the molecular mechanism underlying its antitumor activity is not fully elucidated.
Herein, we have examined the effect of CBD on two different human breast cancer cell lines: the ER-positive, well differentiated, T-47D and the triple negative, poor differentiated, MDA-MB-231 cells.
In both cell lines, CBD inhibited cell survival and induced apoptosis in a dose dependent manner as observed by MTT assay, morphological changes, DNA fragmentation and ELISA apoptosis assay.
CBD-induced apoptosis was accompanied by down-regulation of mTOR, cyclin D1 and up-regulation and localization of PPARγ protein expression in the nuclei and cytoplasmic of the tested cells.
The results suggest that CBD treatment induces an interplay among PPARγ, mTOR and cyclin D1 in favor of apoptosis induction in both ER-positive and triple negative breast cancer cells, proposing CBD as a useful treatment for different breast cancer subtypes.
More (paywalled): https://www.thebreastonline.com/article/S0960-9776(18)30121-8/abstract

The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence (2025)
… Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, using defined keywords such as “CBD,” “lung cancer,” and “non-small cell lung cancer.” Studies from 2007 to 2025 were screened following PRISMA guidelines, and 19 studies met the inclusion criteria.
Results: Nineteen studies met the inclusion criteria, comprising 13 in vitro studies, 4 in vivo animal studies, and 2 clinical reports. Across these studies, CBD was administered at concentrations ranging from low micromolar levels (1-10 µM) in cell-based experiments to oral doses of 200-600 mg/day in human cases. Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress.

CBD also helps our immune system to fight cancer by enhancing CD8+ T cell and NK cell activity:

It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity. Furthermore, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.
Conclusions: CBD holds promise as an adjunct in lung cancer therapy, addressing key cancer hallmarks such as tumor growth, metastasis, and treatment resistance. While preclinical evidence is robust, clinical trials remain limited. Future research should focus on optimizing dosing regimens, evaluating long-term safety, and validating these findings in large-scale human studies.
Keywords: Apoptosis; Cannabidiol (CBD); Combination therapy; EMT; Lung cancer; Non-Small cell lung cancer (NSCLC); Tumor microenvironment.
More: https://pubmed.ncbi.nlm.nih.gov/41126219/

Most exciting is experimental evidence demonstrating that CBD can also target cancer stem cells. Because these cells are untouched by most allopathic drugs, this would significantly decrease the risk of recurrence and of the tumour becoming resistant to treatment:

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells (2021)
Abstract
Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells.
Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells.
We found that CBD decreased viability and induced cell death in both cell populations. Furthermore, we found that CBD activated the effector caspases 3/7, increased the expression of pro-apoptotic proteins, increased the levels of reactive oxygen species, as well as a leading to a loss of mitochondrial membrane potential in both populations.
We also found that CBD decreased self-renewal, a hallmark of cancer stem cells. Overall, our results suggest that CBD is effective against the otherwise treatment-resistant cancer stem cells and joins a growing list of compounds effective against cancer stem cells. The effects and mechanisms of CBD in cancer stem cells should be further explored to find their Achilles heel.
More: https://www.mdpi.com/1424-8247/14/11/1169

For the treatment of demyelinating diseases

The full version of this important paper justifies its own future review:

Cannabidiol and Other Cannabinoids in Demyelinating Diseases (2021)
Abstract
A growing body of preclinical evidence indicates that certain cannabinoids, including cannabidiol (CBD) and synthetic derivatives, may play a role in the myelinating processes and are promising small molecules to be developed as drug candidates for management of demyelinating diseases such as multiple sclerosis (MS), stroke and traumatic brain injury (TBI), which are three of the most prevalent demyelinating disorders.
Thanks to the properties described for CBD and its interesting profile in humans, both the phytocannabinoid and derivatives could be considered as potential candidates for clinical use.
Keywords: cannabinoids, cannabidiol derivatives, demyelinating diseases
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC8001020/

Selected cannabis cultivars modulate glial activation: in vitro and in vivo studies (2024)
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ability to treat MS effectively. However, due to variations in the profile of secondary metabolites, especially cannabinoids, among cannabis cultivars, the effectiveness of cannabis treatment can vary, with significant variability in the effects on different biological parameters.
For screening available cultivars, cellular in vitro as well as pre-clinical in vivo assays, are required to evaluate the effectiveness of the wide range of chemical variability that exists in cannabis cultivars. This study evaluated comparatively three chemically diverse cannabis cultivars, CN2, CN4 and CN6, containing different ratios of phytocannabinoids, for their neuroinflammatory activity in MS model.

The “entourage effect” is beyond the reach of many single-path allopathic drugs, and this is why I would recommend taking CBD not in its pure state, but with the rest of the hundreds of cannabinoids and terpenes that are found in hemp.

Cyclooxygenase (COX-2) enzyme inhibition

Evaluation of the Cyclooxygenase Inhibiting Effects of Six Major Cannabinoids Isolated from Cannabis sativa (2011)
Cyclooxygenase enzymes (COX-1 and COX-2) catalyse the production of prostaglandins from arachidonic acid. Prostaglandins are important mediators in the inflammatory process and their production can be reduced by COX-inhibitors.
Endocannabinoids, endogenous analogues of the plant derived cannabinoids, occur normally in the human body. The Endocannabinoids are structurally similar to arachidonic acid and have been suggested to interfere with the inflammatory process.
They have also been shown to inhibit cancer cell proliferation. Anti-inflammatory effects of cannabinoids and endocannabinoids have been observed, however the mode of action is not yet clarified. Anti-inflammatory activity (i.e., inhibition of COX-2) is proposed to play an important role in the development of colon cancer, which makes this subject interesting to study further.

This study found that both CBD and THC may promote COX1 or COX2 activity in isolation, but the net effect of the major cannabinoids in hemp may be inhibitory.

Cannabigerol (CBG) is a minor constituent of cannabis, and cannabigerolic acid (CBGA) is the acidic form of CBG:

… When screened for COX-2 enzyme inhibiting activity D9THCA-A, CBG and CBGA showed more than 30% inhibition. Interestingly, CBDA, which was recently reported to selectively inhibit COX-2,19) did not reach the 30% inhibition threshold (Fig. 2), and was therefore not considered in our further COX-2 inhibition studies.

A previous paper also associated CBD with inhibitory effects, and the authors highlight contradictory findings about its precursor, CBDA:

In conclusion, it is clear that cannabinoids inhibit COX enzymes, but in a higher concentration range, as compared to anti-inflammatory drugs (i.e. indomethacin). The obvious contradiction regarding the selectivity for CBDA, as compared to the previous report by Takeda et al., 19) is interesting and should be object for further investigation.
Additional studies will also be needed to conclude the relevance of the COX-inhibitory effects in relation to other anti-inflammatory activities mediated by cannabinoids.
As evident from recent reports, the ECS plays an important role in the human body. Interestingly, colonic inflammation can be controlled via the ECS, and plant-derived cannabinoids may have a potential to be used as future therapeutic agents.
More: https://www.jstage.jst.go.jp/article/bpb/34/5/34_5_774/_article

Anti-aging properties

Thanks to their rapid, transparent embryonic development and high genetic homology to humans, zebrafish are a premier vertebrate model organism.

This study found that embryos exposed to low doses of CBD exhibited no signs of teratogenicity, and their lifespans were extended:

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio) (2020)
Abstract
Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown.

Ahem, childhood vaccination effects, anyone?

https://familydoctor.org/wp-content/uploads/2026/04/adolescent-aafp-imm-schedule.pdf

Hep. B, MPOX, Dengue and COVID-19?

Seriously?

They forgot to include Yellow Fever and Ebola.

This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life.
Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later.
F0 exposure to CBD significantly increased survival (~ 20%) and reduced size (wet weight and length) of female fish.
While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 μM CBD significantly reduced sperm concentration in males, but 0.1 μM increased egg production in females.

Kyphosis: An excessive outward curvature of the upper spine that causes a rounded, hunched, or slouching posture (often referred to as a “hunchback”).

Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16^ink4ab, tnfα, il1b, il6, and pparγ) in the liver.
Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls.
The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.

Fig. 1.
Survival (%) measured at 30 months of age of adult F0 zebrafish developmentally exposed to CBD and enrolled into the study at 12 months old. a Male % survival from 12 to 30 months, n = 27–38. b Female % survival from 12 to 30 months, n = 7–13. The number displayed at the base of the bar is the total number of fish per treatment enrolled into the study at 12 months old. Number sign indicates a significant difference compared with aged controls (Fisher’s exact test p ≤ 0.05)

… We observed significant effects on both the health span and longevity of developmentally exposed zebrafish. CBD exposure significantly increased male survival in a concentration-dependent manner, while in females there was only a trending increase. This trend is most likely due to the low sample size of female fish enrolled in the study.

Note that CBD can lower your sperm count, as the endocannabinoid system is necessary for normal sperm function and male fertility:

CBD significantly affected male and female fecundity in a sex-dependent manner.
While a significant reduction in fecundity of both male and female fish was observed due to aging, CBD treatment caused an even further decrease in sperm production relative to the aged-matched controls. These results were similar to our previous study (Carty et al. 2019), where there was a reduction in embryo survival at 24 h post-fertilization in the same population of treated fish when they were 6 months old.
While sperm quantity was not measured in the previous study, 24 h post-fertilization (hpf) survival can be influenced by sperm quality. A reduction of sperm quantity and quality following exposure to CBD has been observed in other animal models including mice and sea urchins (Carvalho et al. 2018; Schuel et al. 1987).
Notably, these exposures were conducted in adolescent or adult organisms, not during embryonic development. The regulation of the endocannabinoid system (ECS) is necessary for normal sperm function and male fertility (Amoako et al. 2013; Battista et al. 2008). For example, seminal plasma N-arachidonoylethanolamide (AEA) levels are lower in men with asthenozoospermia or oligoasthenoteratozoospermia (Amoako et al. 2013).
Given that CBD is known to inhibit both fatty acid amide hydrolyase (FAAH) and fatty acid binding proteins that regulate the degradation of endocannabinoids like AEA, it is possible that embryonic exposure to CBD caused long-term effects within the testes via altered endocannabinoid signaling.
In contrast to the male effects observed in this current study, female fish were partially rescued dose-dependently by treatment of CBD, producing significantly more eggs at the 0.1 μM CBD dose.
Female mice oocytes express several known targets of CBD including G protein coupled receptor 55 (GPR55) and transient vanilloid type 1 channel (TRPV1); antagonism of these receptors can disrupt oogenesis (Cecconi et al. 2019).
The response of increased fecundity at an intermediate concentration in females and reduced sperm at a higher concentration in males suggests a biphasic or hormetic response to CBD for zebrafish reproduction.

… Delayed development due to CBD exposure is supported by the outcome that female CBD-treated fish were significantly smaller, considering both weight and length, than the age-matched controls.
In humans, maternal exposure to cannabis results in infants with lower birth weight (Gunn et al. 2016). In addition, zebrafish exposed to high concentrations (3.2–12.7 μM) of CBD during embryo development resulted in significantly shorter larvae measured at 48 hpf, but the long-term effects on zebrafish growth were not assessed (Ahmed et al. 2018)

… Dietary restriction increases the life and health spans in many eukaryotic species (Adams and Kafaligonul 2018; Beis and Agalou 2020). A restriction in caloric intake, or reduced metabolism, could have contributed to the increased the life span of zebrafish observed in this current study.
Survival correlated strongly with the length of the male and female fish which could imply that treatment groups that ate and grew more had a higher mortality than the treatment groups who did not.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7205952/

Arthritis

There is strong theoretical and experimental evidence in support of the use of cannabinoids both for the treatment of osteoarthritis (OA) and for slowing the rate of progression of the disease.

Although Sci-Hub's uploads of papers from 2022 onwards have been paused by court order, I can highly recommend Anna’s archive for access to full versions of papers that would otherwise be locked behind paywalls, such as this one:

Involvement of the endocannabinoid system in osteoarthritis pain (2014)
Abstract
Osteoarthritis is a degenerative joint disease associated with articular cartilage degradation. The major clinical outcome of osteoarthritis is a complex pain state that includes both nociceptive and neuropathic mechanisms.

Although this paper is 12 years old, there are still no approved drugs which can stop, slow, or reverse the structural progression of OA. All your doctor can do for you is to recommend lifestyle changes, and help manage the pain and reduce inflammation, usually with steroids and NSAIDs.

Currently, the therapeutic approaches for osteoarthritis are limited as no drugs are available to control the disease progression and the analgesic treatment has restricted efficacy. Increasing evidence from preclinical studies supports the interest of the endocannabinoid system as an emerging therapeutic target for osteoarthritis pain.

Nociceptive: the sensory nervous system's process of encoding noxious stimuli, usually perceived as pain signals to the brain, to prompt a defensive reaction:

Indeed, pharmacological studies have shown the anti-nociceptive effects of cannabinoids in different rodent models of osteoarthritis, and compelling evidence suggests an active participation of the endocannabinoid system in the pathophysiology of this disease.
The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the endocannabinoid system in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis.
However, limited clinical evidence has been provided to support this therapeutic use of cannabinoids, despite the promising preclinical data. This review summarizes the promising results that have been recently obtained in support of the therapeutic value of cannabinoids for osteoarthritis management.

Endocannabinoid system and osteoarthritis
The major clinical outcome of osteoarthritis is a complex pain state that includes manifestations of both nociceptive and neuropathic mechanisms. Several findings support the interest of the endocannabinoid system as an emerging therapeutic option for osteoarthritis.
Indeed, recent studies have demonstrated the anti-nociceptive effects of both CB1R and CB2R agonists in rodent models of osteoarthritis (Schuelert & McDougall, 2008; Yao et al., 2008). In agreement, knee joints possess an active endocannabinoid system (Schuelert & McDougall, 2008; Schuelert et al., 2011) that contributes to the regulation of synovial blood flow and joint pain (McDougall et al., 2008; Schuelert & McDougall, 2008; Schuelert et al., 2010).
Moreover, the putative presence of cannabinoid receptors on chondrocytes (Mbvundula et al., 2006) and bone (Idris & Ralston, 2012) suggests a possible role of cannabinoids in regulating cartilage breakdown and bone remodelling processes that take place during osteoarthritis.

Pharmacological modulation of osteoarthritis pain by cannabinoids
Recent behavioural and electrophysiological studies have demonstrated that cannabinoids exert anti-nociceptive effects in rodent models of osteoarthritis (Schuelert & McDougall, 2008; Yao et al., 2008; Table 2). The local administration of the CB1R agonist, arachidonyl-2-chloroethylamide (ACEA), into the knee joint reduced the hypersensitivity of afferent nociceptors in the rat MIA model by a mechanism involving CB1R and transient receptor potential vanilloid-1 (TRPV-1) channel (Schuelert & McDougall, 2008).
Interestingly, ACEA anti-nociception was greater in the osteoarthritis joints compared with control joints (Schuelert & McDougall, 2008). In addition, the intra-articular application of a CB1R antagonist alone increased the activity of afferent nerve fibres in the osteoarthritic joint, but not in the control joint, suggesting a tonic release of endocannabinoids at the joint level during osteoarthritis (Schuelert & McDougall, 2008).

… Cannabinoids exert both immunosuppressive and anti-inflammatory actions by mechanisms that include effects on apoptosis, inflammatory cell proliferation and trafficking, cytokine production and regulatory T-cells (Rieder et al., 2010).
In agreement, the non-psychoactive cannabis constituent cannabidiol (Malfait et al., 2000) and the synthetic non-psychoactive cannabinoid acid HU-320 (Sumariwalla et al., 2004) showed immunosuppressive, anti-inflammatory and anti-arthritic effects in the murine collagen-induced arthritis.
In addition, ajulemic acid, a synthetic derivative of D9-tetrahydrocannabinol (THC), reduced the severity of adjuvant-induced arthritis (Zurier et al., 1998, 2003) by a mechanism involving the peroxisome proliferator-activated receptor-c (Liu et al., 2003).

… The presence of local joint inflammation and altered cartilage and bone turnover in osteoarthritis implicates a great variety of pain mechanisms that can be influenced by non-cartilaginous structures in the joint (synovium and bone), as the cartilage is an avascular and aneural tissue (Sofat et al., 2011). Cannabinoids exert a direct effect on chondrocytes, synovium and bone metabolism, which reveals an attractive therapeutic potential.
Synthetic cannabinoids showed protective effects toward cytokine-induced extracellular matrix degradation in cartilage through the inhibition of the synthesizing enzymes of inflammatory mediators, such as prostaglandin E2 (PGE2) and NO (Mbvundula et al., 2005, 2006).
Excessive PGE2 and NO production are involved in the aetiopathogenesis of osteoarthritis (Henrotin et al., 2003; Martel-Pelletier et al., 2003). Therefore, cannabinoids could have a modulatory effect on the early stages and progression of osteoarthritis disease.
More: https://annas-archive.gl/scidb/10.1111/ejn.12468/

A 2016 study of articular cartilage from patients with systemic osteoarthritis confirmed the presence of cannabinoid receptors, even in degenerate tissue, thereby supporting their potential as therapeutic targets.

Chondrocytes are the only cells found in healthy cartilage. They’re responsible for producing and maintaining the extracellular matrix (ECM), which gives cartilage its flexibility and shock-absorbent properties.

Expression of Cannabinoid Receptors in Human Osteoarthritic Cartilage: Implications for Future Therapies (2016)
Abstract
Introduction: Cannabinoids have shown to reduce joint damage in animal models of arthritis and reduce matrix metalloproteinase expression in primary human osteoarthritic (OA) chondrocytes.
The actions of cannabinoids are mediated by a number of receptors, including cannabinoid receptors 1 and 2 (CB1 and CB2), G-protein-coupled receptors 55 and 18 (GPR55 and GPR18), transient receptor potential vanilloid-1 (TRPV1), and peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ).
However, to date very few studies have investigated the expression and localization of these receptors in human chondrocytes, and expression during degeneration, and thus their potential in clinical applications is unknown.
Methods: Human articular cartilage from patients with symptomatic OA was graded histologically and the expression and localization of cannabinoid receptors within OA cartilage and underlying bone were determined immunohistochemically. Expression levels across regions of cartilage and changes with degeneration were investigated.
Results: Expression of all the cannabinoid receptors investigated was observed with no change with grade of degeneration seen in the expression of CB1, CB2, GPR55, PPARα, and PPARγ. Conversely, the number of chondrocytes within the deep zone of cartilage displaying immunopositivity for GPR18 and TRPV1 was significantly decreased in degenerate cartilage. Receptor expression was higher in chondrocytes than in osteocytes in the underlying bone.
Conclusions: Chondrocytes from OA joints were shown to express a wide range of cannabinoid receptors even in degenerate tissues, demonstrating that these cells could respond to cannabinoids. Cannabinoids designed to bind to receptors inhibiting the catabolic and pain pathways within the arthritic joint, while avoiding psychoactive effects, could provide potential arthritis therapies.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC5576594/

A systems biology approach, and the use of CBD for the prevention and treatment of kidney disease

Analysis of the mechanisms of CBD in isolation will not give you the full picture of its many potential systemic therapeutic properties. Rather than asking if it has any effect at all, it’s more a case of asking how beneficial it might be for a condition. And so it is with kidney disease, as I found in my literature search.

CBD isn’t free of negative side effects, but these are usually relatively mild or manageable:

Digestive Discomfort
Fatigue and Somnolence
Dry Mouth
Drug-Drug Interactions
Liver Enzyme Elevation

You need to use a systems biology approach to help to grasp all the mechanisms and systemic interactions.

According to Wikipedia:

Systems biology is the computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological systems, using a holistic approach (holism instead of the more traditional reductionism) to biological research.^[1]

This multifaceted research domain necessitates the collaborative efforts of chemists, biologists, mathematicians, physicists, and engineers to decipher the biology of intricate living systems by merging various quantitative molecular measurements with carefully constructed mathematical models.

It represents a comprehensive method for comprehending the complex relationships within biological systems. In contrast to conventional biological studies that typically center on isolated elements, systems biology seeks to combine different biological data to create models that illustrate and elucidate the dynamic interactions within a system.

This methodology is essential for understanding the complex networks of genes, proteins, and metabolites that influence cellular activities and the traits of organisms.^[2]^[3]

One of the aims of systems biology is to model and discover emergent properties, of cells, tissues and organisms functioning as a system whose theoretical description is only possible using techniques of systems biology.^[1]^[4]

By exploring how function emerges from dynamic interactions, systems biology bridges the gaps that exist between molecules and physiological processes.

A systems biology approach is starting to be used in CBD research:

Computational systems pharmacology analysis of cannabidiol: a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation (2019)
Abstract
With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers.
In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the in silico analysis and the reported experimental validations.
Based on the network analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5-hydroxytryptamine receptor 1 A (5HT_1A), delta-type opioid receptor (OPRD) and G protein-coupled receptor 55 (GPR55), were selected for close evaluation.
Integrated computational methodologies, including homology modeling, molecular docking, and molecular dynamics simulation, were used to evaluate the protein-CBD binding modes.
A CBD-preferred pocket consisting of a hydrophobic cavity and backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally, the neurophysiological effects of CBD were illustrated at the molecular level, and dopamine receptor 3 (DRD3) was further predicted to be an active target for CBD.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC6460368/

This study, which used rats, found that CBD could be used to control renal problems by targeting levels of a localised cytokine (IL-6) that helps to signal nephrotoxic pro-inflammatory immune responses.

They used a nephrotoxic chemotherapy drug called doxorubicin to induce the kidney damage:

Prospective affirmative therapeutics of cannabidiol oil mitigates doxorubicin-induced abnormalities in kidney function, inflammation, and renal tissue changes (2023)
Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection.
The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V).
The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results.
As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.

They used the levels of TNF and the inflammatory cytokine IL-6 as markers for inflammation, and the effects of CBD were dramatic:

For upregulation to the expression of IL6R in a group of doxorubicin in comparison with control and other groups, Nechemia-Arbely et al. (2008) showed that renal autoimmune and inflammatory disorders are associated with local activation of the IL-6 classic and trans-signaling pathway.
Under some conditions, kidney resident cells such as podocytes, endothelial cells, mesangial cells, and tubular epithelial cells (TECs) can release IL-6. The only resident cell that expresses IL-6R is the podocyte; all other cells lack this receptor and lack typical IL-6 signaling.
Renal IL-6 mRNA expression rose in mice with either AKI or CKD, indicating the kidney is the source of the elevated serum IL-6 levels in the uremic state by our results of upregulation to IL6R frequency concentration. Circulating sIL-6R levels increased in both conditions of CKD and AKI mice (Durlacher-Betzer et al. 2018).
In the damage progression, renal IL-6 expression and STAT3 activation considerably increased in renal tubular epithelial cells, indicating active IL-6 signaling. IL-6 can stimulate target cells when combined with a soluble form of the IL-6R (sIL-6R), a method known as trans-signaling, even if the absence of renal IL-6 receptors (IL-6R) prevents the activation of conventional signaling pathways. The three-fold rise in serum sIL-6R levels during injury raises the possibility that IL-6 trans-signaling plays a part in AKI (Chen et al. 2019).

They found that CBD oil was better at protecting the kidneys than the anti-angina medication, Trimetazidine (TMZ). Although its primary function is to protect cardiac tissues from damage caused by hypoxia (hemorrhagic shock, HS), it also helps to protect kidney function as a secondary benefit:

Conclusions and prospects for the future
The antioxidant and anti-inflammatory properties of cannabidiol oil may be the reason for its potential renal protective effects in comparison with other drugs (trimetazidine). Biochemical, oxidative, and histological investigations of cannabidiol demonstrated its antioxidant activity and kidney protection.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC11111484/

Cardiovascular disease and hypertension: vasodilatory effects

You may not be imagining it, if you find that your circulation improves and your BP falls after taking CBD.

Despite media coverage to the contrary, lifetime cannabis use is not associated with increased hypertension and coronary artery disease risk.9 On the contrary, the opposite is true due to its vasodilatory, antioxidant, and anti-inflammatory properties.

Vasodilatory effects of cannabidiol in human pulmonary and rat small mesenteric arteries: modification by hypertension and the potential pharmacological opportunities (2019)
Abstract
Objective:
Cannabidiol (CBD) has been suggested as a potential antihypertensive drug. The aim of our study was to investigate its vasodilatory effect in isolated human pulmonary arteries (hPAs) and rat small mesenteric arteries (sMAs).
Methods:
Vascular effects of CBD were examined in hPAs obtained from patients during resection of lung carcinoma and sMAs isolated from spontaneously hypertensive (SHR); 11-deoxycorticosterone acetate (DOCA-salt) hypertensive rats or their appropriate normotensive controls using organ bath and wire myography, respectively.
Results:
CBD induced almost full concentration-dependent vasorelaxation in hPAs and rat sMAs. In hPAs, it was insensitive to antagonists of CB₁ (AM251) and CB₂ (AM630) receptors but it was reduced by endothelium denudation, cyclooxygenase inhibitors (indomethacin and nimesulide), antagonists of prostanoid EP₄ (L161982), IP (Cay10441), vanilloid TRPV1 (capsazepine) receptors and was less potent under KCl-induced tone and calcium-activated potassium channel (K_Ca) inhibitors (iberiotoxin, UCL1684 and TRAM-34) and in hypertensive, overweight and hypercholesteremic patients.
The time-dependent effect of CBD was sensitive to the PPARγ receptor antagonist GW9662. In rats, the CBD potency was enhanced in DOCA-salt and attenuated in SHR. The CBD-induced relaxation was inhibited in SHR and DOCA-salt by AM251 and only in DOCA-salt by AM630 and endothelium denudation.
Conclusion:
The CBD-induced relaxation in hPAs that was reduced in hypertensive, obese and hypercholesteremic patients was endothelium-dependent and mediated via K_Ca and IP, EP₄, TRPV1 receptors. The CBD effect in rats was CB₁-sensitive and dependent on the hypertension model. Thus, modification of CBD-mediated responses in disease should be considered when CBD is used for therapeutic purposes.

The findings were replicated using human pulmonary arteries and rat small mesenteric arteries (sMAs).

Lower is better:

FIGURE 1.
Influence of cannabidiol (10 μmol/l) on the concentration--response curve of U46619-induced contraction (a), its vasodilatory effect in endothelium-intact isolated human pulmonary arteries (b; c -- representative original trace) and post hoc analysis of the patients comorbidities on cannabidiol-mediated vasorelaxation (d–f).
^∗P less than 0.05 according to Student's t-test. The results are presented as the mean ± SEM of n tissue samples for each curve. See Table 1 for n and the statistical analysis (b). The control curve for cannabidiol vehicle [ethanol, 0.1% v/v (a) and 0.001 – 0.3% v/v final concentration (b), respectively]. In a few cases, SEM is smaller than or equal to the size of symbols. Arrows show the moment of application of a particular concentration of CBD. CBD, cannabidiol. hPAs, human pulmonary arteries.

CBD (0.1–30 μmol/l) but not its vehicle caused almost full relaxation of the hPAs preconstricted with U46619 (Fig. 1b); the pEC₂₅ and pEC₅₀ values were 5.8 and 5.0, respectively (Table 2). The vehicle controls with CBD were comparable (ethanol, pEC₅₀ = 5.0 ± 0.1, n = 5; DMSO, 5.0 ± 0.1, n = 6; water, pEC₅₀ = 4.9 ± 0.1, n = 10). They are presented in the Figures as one merged control group (pEC₅₀ = 5.0 ± 0.1, n = 21). The vasodilatation induced by CBD was gradual in onset. Thus, it took 80 min to construct the whole CRCs (for the original traces see Fig. 1c).
The vasodilator responses to CBD varied between patients (the maximal response to CBD ranged from 63 to 120% relaxation), so post hoc analysis was performed to establish any relationships between CBD responses and patient characteristics (see Table 1).

Although the potency of CBD was reduced by hypertension and hypercholesteraemia, the maximal response was only diminished in obese patients. Thus, CBD is highly effective for most recipients:

The potency of CBD was reduced by hypertension (vs. normotension; pEC₅₀ = 4.1 ± 0.3, n = 8 vs. 4.9 ± 0.1, n = 13, P < 0.05; Fig. 1d), obesity (vs. lean; pEC₅₀ = 4.4 ± 0.1, n = 7 vs. 5.0 ± 0.1, n = 14, P < 0.01; Fig. 1e) and hypercholesteraemia (vs. normocholesteraemia; pEC₅₀ = 4.4 ± 0.2, n = 8 vs. 5.0 ± 0.1, n = 13, P < 0.01; Fig. 1f), whereas the maximal response was diminished only in obese patients (R_max = 76.6 ± 5.0, n = 7 vs. 93.2 ± 4.8, n = 14, P < 0.05; Fig. 1e).

β-blockers helped to cancel out its beneficial effects, but other drugs or conditions didn’t attenuate its action:

Moreover, the vasorelaxation to lower concentrations of CBD was attenuated in those taking β-blockers (vs. no β-blockers; pEC₂₅ = 5.9 ± 0.1, n = 8 vs. 5.5 ± 0.1, n = 13; P < 0.01; no differences in pEC₅₀ values).
The following parameters, concurrent diseases and cardiovascular therapy had no influence on the CBD-evoked relaxation: sex, age, smoking, prevalence of chronic obstructive pulmonary disease, type 2 diabetes and angiotensin-converting enzyme inhibitors, α₁-adrenolytics statins, nonsteroidal anti-inflammatory drugs (NSAIDs and proton pump inhibitors (PPIs) (for pEC₅₀ and R_max see Table 1).
In a few cases, coronary artery disease, angiotensin receptor blockers, calcium channel blockers and hypoglycaemics virtually did not change CBD-mediated effects, however patient numbers were too small for adequate statistical analysis.

The present study demonstrated a potent influence of CBD in the regulation of vascular tone in pulmonary circulation of human and that it could be modified by disease, including hypertension.
The vasorelaxant effects of CBD in hPAs preconstricted with thromboxane analogue, U46619 is endothelium-dependent and include the following mechanisms: IP, EP₄, TRPV1, PPARγ receptors and K_Ca channels.
We have also shown species-specific, vascular-bed-specific and hypertension model differences in response to CBD, as in phenylephrine-preconstricted rat sMAs, CBD-evoked vasorelaxation was enhanced in DOCA-salt but diminished in SHR compared with respective normotensive controls.

Rat models may not fully reflect the effects on humans:

Moreover, in rats but not in humans, CB₁ receptors could play potential protective role in both models of hypertension. Our findings provide evidence that CBD could be a potential relevant vasorelaxant; however, modification of its responses in disease should be considered whenever CBD is used for therapeutic purposes.

Conclusion and perspectives
In conclusion, our results demonstrate that CBD caused a full concentration-dependent and endothelium-dependent relaxation of hPAs. This was mediated through IP, EP₄ and TRPV1 receptors and K_Ca channels.
Moreover, CBD produced a time-dependent slowly developing decrease in the tone of endothelium-intact hPAs sensitive to the PPARγ antagonist, GW9662. Pulmonary hypertension is a life-threatening condition that lacks effective therapy.
The following facts underline the possibility that CBD might represent a future goal/option in the therapy of this disease that had been previously suggested to abn-CBD [22]: the strong vasorelaxant efficacy of CBD in hPAs is dependent among others on IP receptors, prostacyclin analogues belong to the frontline therapy against pulmonary hypertension [58] and inhalation is the main route of cannabinoid administration.
… In light of the evidence that CBD could reduce BP in stressed patients, our data supplies a further rationale that the cardiovascular system could be indeed a valid therapeutic target for CBD and that preclinical responses to CBD will translate into the human cardiovascular system.
Thus, CBD-derived therapies after years might have potential for the evaluation and development of CBD-based drugs not only for neuronal disorders but also in cardiovascular diseases.
Importantly, CBD is a nonpsychotropic drug and it has been demonstrated to offer well tolerated therapy. Overall, our results suggest that although the beneficial effects of CBD in cardiovascular disorders are known, additional studies are required to fully understand its potential contributions in the clinical setting [1].
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC7170434/

Therapeutic potential of cannabidiol (CBD) in the treatment of cardiovascular diseases (2024)
ABSTRACT
Introduction
Cannabidiol (CBD) is the primary non-psychoactive chemical derived from Cannabis Sativa, and its growing popularity is due to its potential therapeutic properties while avoiding the psychotropic effects of other phytocannabinoids, such as tetrahydrocannabinol (THC).
Numerous pre-clinical studies in cellular and animal models and human clinical trials have demonstrated a positive impact of CBD on physiological and pathological processes. Recently, the FDA approved its use for the treatment of seizures, and clinical trials to test the efficacy of CBD in myocarditis and pericarditis are ongoing.
Areas covered
We herein reviewed the current literature on the reported effects of CBD in the cardiovascular system, highlighting the physiological effects and the outcomes of using CBD as a therapeutic tool in pathological conditions to address this significant global health concern.
Expert opinion
The comprehensive examination of the literature emphasizes the potential of CBD as a therapeutic option for treating cardiovascular diseases through its anti-inflammatory, vasodilatory, anti-fibrotic, and antioxidant properties in different conditions such as diabetic cardiomyopathy, myocarditis, doxorubicin-induced cardiotoxicity, and ischemia-reperfusion injury.
Article highlights
The US Food and Drug Administration (FDA) approved the use of a highly purified Cannabidiol (CBD) formulation to be given orally for treating seizures associated with Dravet and Lennox-Gastaut.
CBD has been extensively tested in animal disease models and several clinical trials in patients with different diseases, such as neurological disorders, inflammatory diseases and pain, kidney disease, metabolic disease, cardiovascular diseases, and Coronavirus Disease- 2019.
Benefits of CBD in treating cardiovascular diseases are due to physiological factors, like the observed blood pressure-lowering effects, its antioxidant and anti-fibrotic effect, and its anti-inflammatory activity.
The effects of CBD are multiple, and rigorous pre-clinical and clinical testing are warranted to gain from its therapeutic potential in each specific disease and offset possible undesired effects.
CBD has shown cardioprotective effects in different endpoints in animal models of myocardial ischemia-reperfusion injury, doxorubicin cardiotoxicity, arrhythmias, myocarditis, pericarditis, and diabetic cardiomyopathy. Most importantly, two clinical trials are being performed to assess its effectiveness on pericarditis and myocarditis in humans.
More (paywalled): https://www.tandfonline.com/doi/10.1080/13543784.2024.2351513

Honourary mention:

Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB₁ activation (2015)
Abstract
Aims
The protective effects of cannabidiol (CBD) have been widely shown in preclinical models and have translated into medicines for the treatment of multiple sclerosis and epilepsy. However, the direct vascular effects of CBD in humans are unknown.
Methods and results
Using wire myography, the vascular effects of CBD were assessed in human mesenteric arteries, and the mechanisms of action probed pharmacologically. CBD-induced intracellular signalling was characterized using human aortic endothelial cells (HAECs). CBD caused acute, non-recoverable vasorelaxation of human mesenteric arteries with an R_max of ∼40%.
This was inhibited by cannabinoid receptor 1 (CB₁) receptor antagonists, desensitization of transient receptor potential channels using capsaicin, removal of the endothelium, and inhibition of potassium efflux.
There was no role for cannabinoid receptor-2 (CB₂) receptor, peroxisome proliferator activated receptor (PPAR)γ, the novel endothelial cannabinoid receptor (CB_e), or cyclooxygenase. CBD-induced vasorelaxation was blunted in males, and in patients with type 2 diabetes or hypercholesterolemia.
In HAECs, CBD significantly reduced phosphorylated JNK, NFκB, p70s6 K and STAT5, and significantly increased phosphorylated CREB, ERK1/2, and Akt levels. CBD also increased phosphorylated eNOS (ser1177), which was correlated with increased levels of ERK1/2 and Akt levels. CB₁ receptor antagonism prevented the increase in eNOS phosphorylation.
Conclusion
This study shows, for the first time, that CBD causes vasorelaxation of human mesenteric arteries via activation of CB₁ and TRP channels, and is endothelium- and nitric oxide-dependent.

Figure 1.
CBD relaxes human mesenteric arteries. Typical trace data showing the acute (A) and time-dependent (B) vasorelaxant effects of CBD (also in the presence of the PPARgamma antagonist GW9662) in the human mesenteric artery. (C) Mean (± SEM, n = 12) concentration-response curves to CBD compared with vehicle controls carried out in adjacent segments of mesenteric artery from the same patient. The vasorelaxant response to 10 µmol/L bradykinin in the same patients is shown for comparison. (D) Mean time-dependent vasorelaxant response to a single concentration of CBD (10 µmol/L) compared with vehicle controls carried out in adjacent segments of mesenteric artery (n = 6). R_max and EC₅₀ values were compared by paired Students t-test, *P < 0.05, ****P < 0.0001.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC4540144/

We’ve seen the lab results, but what does this mean in reality?

A clinical study from 2017 reported a measured decrease in resting systolic blood pressure (SBP) of about 6 mmHg after a single dose of CBD.10

This is comparable to, or even superior to, the effects of taking a common ACE inhibitor, Ramipril, which is not in the same league as CBD:

Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures: A HOPE Substudy (2001)
Abstract
In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP.
Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients.
Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four–hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001).
The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime.
Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.
More: https://www.ahajournals.org/doi/10.1161/01.HYP.0000184527.20503.98

Note: As per the disclaimer, do not cast your meds aside without seeking the advice of your physician or other qualified health provider first.

An excellent review published at the start of 2026 goes further, suggesting that CBD may be useful for treating recurrent pericarditis too:

Cannabidiol in Cardiovascular Disease: A Review of Current Evidence and Future Directions (2026)
Article Highlights
CBD reduces pericardial inflammation in preclinical models, with the MAVERIC-Pilot trial showing significant pain reduction in recurrent pericarditis.
CBD may emerge as a novel, nonimmunosuppressive therapeutic option for recurrent pericarditis, offering an alternative to corticosteroids and IL-1 inhibitors.
CBD protects against ischemia-reperfusion injury in preclinical studies, reducing infarct size by 66% and improving myocardial recovery in animal models.
CBD has shown antihypertensive effects, lowering 24-hour ambulatory blood pressure in a randomized controlled trial of hypertensive patients.
The clinical adoption of CBD in cardiovascular disease is challenged by lack of standardized dosing, potential drug interactions, and regulatory barriers.

Transient Receptor Potential (TRP) channels are integral membrane proteins that act as vital cellular sensors. Their main function is to convert environmental physical and chemical signals into biochemical changes—primarily by altering the membrane potential or increasing intracellular calcium (Ca²⁺) concentrations.

In the cardiovascular system, this is reflected in vascular muscle tone and endothelial function.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a ligand-activated transcription factor and a master regulator of cellular metabolism, adipogenesis (fat cell differentiation), and inflammatory responses. It plays an indispensable role in maintaining systemic energy homeostasis and insulin sensitivity.

Figure 1. Comparative properties of tetrahydrocannabinol (THC) and cannabidiol (CBD). CB1/2, cannabidiol receptor type 1/2; PPARγ, peroxisome proliferator-activated receptor gamma; TRP, transient receptor potential.
Preclinical studies have shown that CBD affects several key pathways relevant to cardiovascular health. More specifically, it activates transient receptor potential (TRP) channels, which are involved in vascular tone and endothelial function, and peroxisome proliferator-activated receptor gamma (PPARγ), which regulates inflammation and lipid metabolism.¹
Cannabidiol has also been shown to reduce oxidative stress, a major contributor to endothelial dysfunction and cardiovascular disease progression.^2. These mechanisms, coupled with their favorable safety profile, position CBD as a promising candidate for managing cardiovascular diseases driven by inflammation and oxidative stress including IHD, heart failure, and pericarditis.

Figure 2. Core mechanisms through which cannabidiol exerts anti-inflammatory, vasodilatory, and cardioprotective effects in cardiovascular disease. CB2, cannabidiol receptor type 2; CBD, cannabidiol; IL, interleukin; NF-κB, nuclear factor kappa-light chain-enhancer of activated B cells; NLRP3, NACHT, LRR, and PYD domains-containing protein 3; TNF-α, tumor necrosis factor- α; TRPV1, transient receptor potential vanilloid 1.

Inhibiting IL-1 is drastic and can have severe consequences, as it’s a master regulator of local and systemic inflammation and a crucial molecular communicator within the immune system.

It helps activate our innate immune defences in response to injury or infection and acts as a bridge to adaptive immunity. IL-1 helps with tissue repair through the stimulation of fibroblasts, and it’s involved with lipid metabolism and essential bone remodelling.

Pericarditis
Acute pericarditis, characterized by inflammation of the pericardial layers encasing the heart, is the most prevalent pericardial disease (Figure 3). Management strategies primarily involve nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids.²¹
Following initial symptom improvement, a subset of patients may experience recurrent pericarditis, necessitating the use of IL-1 inhibitors as a therapeutic option for those unresponsive to previous therapies.
Recurrent pericarditis presents an ongoing therapeutic challenge for clinicians, particularly in cases where patients do not respond to triple therapy, which includes steroids.²² The potent anti-inflammatory effects of CBD have led to its consideration as a potential therapeutic agent for this condition.

Clinical trials are ongoing to investigate CBD’s value in treating myocarditis, too:

… Lee et al²⁶ evaluated the efficacy of CBD in animal models of autoimmune myocarditis showing that CBD attenuated myocardial inflammation and dysfunction through its anti-inflammatory and antifibrotic effects.
Histologic analysis of hematoxylin and eosin–stained myocardial sections revealed a significant reduction in inflammatory cell infiltration following CBD treatment, accompanied by decreased mRNA expression of CD4, CD8, IL-1β, and IL-6.
By reducing oxidative stress and fibrosis and promoting sarco/endoplasmic reticulum calcium ATPase mRNA expression, CBD treatment led to substantial improvements in both systolic and diastolic cardiac function, quantified by volume conductance catheter.²⁶
TheAcute myocaRditis Cannabidiol tHERapy (ARCHER) trial is an ongoing randomized, double-blind, placebo-controlled phase II study designed to assess the safety and efficacy of CBD in patients with mild to moderate acute myocarditis. Patients meeting predefined criteria for acute myocarditis were randomized to receive CBD or placebo, in addition to standard heart failure therapies. While results have not yet been reported, the ARCHER trial stands as the first randomized study of CBD in myocarditis and will be central in determining its potential role in management.²⁷
Emerging preclinical evidence suggests that CBD suppresses inflammatory cell infiltration, leading to reduced myocardial inflammation and fibrosis in autoimmune myocarditis. The applicability of this effect beyond autoimmune models, particularly to viral and idiopathic forms, has not been established and requires further study. Given the limited treatment options for myocarditis, large multicenter randomized control trials are crucial to evaluate the therapeutic potential of CBD and determining its viability as a novel treatment approach.

It shows promise for treating heart failure and myocardial injury, including potential reversal of diabetes-associated pathologies:

Several studies investigating the effects of CBD on myocardial injury have focused on its potential role in diabetic cardiomyopathy. Chronic hyperglycemia contributes to endothelial dysfunction, heightened oxidative stress, and the formation of advanced glycosylation end products, leading to pathological alterations in myocardial structure and function.³
Cannabidiol has been shown to attenuate hyperglycemia-induced mitochondrial superoxide production, NF-κB activation and nitrotyrosine formation in human cardiomyocytes, all of which are key pathological mechanisms in the progression of this disease.⁴
Additionally, CBD treatment reversed diabetes-induced myocardial biochemical and functional alterations, even after the establishment of diabetic cardiomyopathy and fibrosis in mouse models.⁵ Although these findings are promising, clinical trials are needed to determine whether these effects translate into meaningful therapeutic benefits for patients with this condition.

Hypertension
… In human studies, CBD was reported to induce vasorelaxation of the human mesenteric artery using wire myography, mediated by cannabinoid receptor and TRP channels.⁴² Additionally, a randomized, placebo-controlled crossover study including 70 patients with mild to moderate hypertension found that CBD significantly reduced 24-hour ambulatory mean, systolic, and diastolic blood pressure after 2.5 weeks (P<.05).
Cannabidiol was administered at a maximum dose of 5 mg/kg/d for 5 weeks and no serious adverse effects were reported.⁴³ A smaller study investigating the effects of a single 600-mg CBD dose in nine healthy volunteers showed a significant reduction in resting systolic blood pressure (decrease in 6 mm Hg; P<.05) while attenuating the blood pressure response to mental, exercise, and cold stress. Post hoc analysis also revealed reductions in mean arterial pressure, diastolic pressure, total peripheral vascular resistance, and stroke volume following administration.⁴⁴
These findings suggest that CBD exerts favorable, albeit modest blood pressure reduction. However, whether these effects are substantial enough to yield clinically significant cardiovascular benefits remains unclear. Given the potential contribution of anxiolytic mechanisms, the modest blood-pressure effects observed to date cannot be ascribed to direct vascular actions, underscoring the need for mechanistic endpoints in future trials.
More: https://www.sciencedirect.com/science/article/pii/S002561962500566X#bib44

Cutaneous wound healing

The cost of wound care under Medicare approached $100B in 2018.

This study supports the potential use of CBD to improve diabetic cutaneous wound healing:

Cutaneous Wound Healing and the Effects of Cannabidiol (2024)
Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%.
Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries.
To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems.

They found that CBD more than doubled the levels in diabetic mice of a type of cell that produces connective tissue growth factor, CTGF, thus promoting healing:

… We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM).
The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing.
We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model.
… CBD may have some beneficial effects in diabetic wounds. We applied 6–mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle.
The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.

1.4C. The Role of CTGF
Connective Tissue Growth Factor (CTGF), a multifunctional and dynamic protein, plays a pivotal role in orchestrating the cellular and molecular events during the healing process [73]. A CTGF acts as a central hub that integrates signals from various growth factors, cytokines, and extracellular matrix components.
Its multifaceted interactions enable CTGFs to modulate cellular responses critical for the healing cascade. From stimulating fibroblast proliferation to influencing extracellular matrix production, CTGFs stand at the crossroads of cellular activities that drive tissue repair [95,96,97].
The extracellular matrix (ECM) serves as the architectural scaffold for tissue regeneration, and CTGF is a key player in its remodeling. By promoting the synthesis of ECM components such as collagen and fibronectin, a CTGF contributes to the formation of a supportive microenvironment for cell migration, adhesion, and tissue restructuring. This role is particularly crucial in wound healing and tissue regeneration [98].
CTGF’s influence extends to the realm of angiogenesis, the formation of new blood vessels. As an angiogenic factor, a CTGF facilitates the recruitment and proliferation of endothelial cells, fostering the development of a robust vascular network essential for nutrient and oxygen delivery to healing tissues [99,100]. The angiogenic properties of CTGFs are integral to their role in both physiological and pathological healing contexts.
Fibroblasts are pivotal in tissue repair, and CTGFs actively influence the differentiation of mesenchymal stem cells to differentiate into fibroblasts [101]. Also, this growth factor can activate fibroblasts and promote their differentiation into myofibroblasts, which contributes to wound contraction and the synthesis of contractile proteins, ensuring the mechanical integrity of healing tissues [102].

Diabetics produce the same amount of CTGFs, but their rate of degradation in a wound is higher because they have higher levels of a kinase that breaks down proteins, including CTGFs: matrix metalloproteinases (MMPs).

As early as 2015, using a wound model in non-human primates, Thomson et al. documented lower levels of intact CTGFs in diabetic baboons’ incisional wounds even though the CTGF mRNA levels were identical between diabetic and non-diabetic animals, indicating increased degradation in the diabetic wounds [103].
The two-fold increase at week 4 after wounding in TIMP-1 levels of non-diabetic baboons confirmed the low CTGF was not due to a lack of production but the result of excessive breakdown as the MMPs were not under sufficient inhibition.
Understanding the intricate role of CTGFs in the healing process opens avenues for therapeutic interventions. Targeting CTGF pathways could hold promise in modulating tissue repair dynamics, particularly in cases of impaired wound healing or fibrotic disorders.
It is also important to better understand the influence of CBD on CTGF pathways and how it can be used in wound healing management since it is an easy and inexpensive treatment.
Our lab has been exploring the potential of CBD as a CTGF enhancer to fine-tune its activities, offering new possibilities for precision medicine in the context of tissue regeneration and repair.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC11241632/

This study suggests that the “topical application of cannabinoids may be a potential therapeutic option for postsurgical and chronic wounds”:

The effect of cannabinoids on wound healing: A review (2024)
Abstract
Background and Aims
Cannabis and its various derivatives are commonly used for both recreational and medicinal purposes. Cannabinoids have been shown to have anti‐inflammatory properties. Inflammation is an important component of wound healing and the effect of cannabinoids on wound healing has become a recent topic of investigation. The objective of this article is to perform a comprehensive review of the literature to summarize the effects of cannabinoids on wound healing of the skin and to guide future avenues of research.
Methods
A comprehensive literature review was performed to evaluate the effects of cannabinoids on cutaneous wound healing.
Results
Cannabinoids appear to improve skin wound healing through a variety of mechanisms. This is supported through a variety of in vitro and animal studies. Animal studies suggest application of cannabinoids may improve the healing of postsurgical and chronic wounds.
There are few human studies which evaluate the effects of cannabinoids on wound healing and many of these are case series and observational studies. They do suggest cannabinoids may have some benefit. However, definitive conclusions cannot be drawn from them.
Conclusion
While further human studies are needed, topical application of cannabinoids may be a potential therapeutic option for postsurgical and chronic wounds.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC10895075/

2.5 The entourage effect

Why full-spectrum plant extracts are superior to single-compound extracts:

Cannabis sativa L. has been used as medicine for thousands of years. Since the early identification of tetrahydrocannabinol (THC) in 1960, pharmacological activities were attributed to a group of unique structures named cannabinoids. For decades, research and development were applied to determine different cannabinoids and their medicinal properties.

Nowadays there is evidence that the therapeutic benefits of the plant are based on the synergy of cannabinoids and other secondary metabolites such as terpenes and flavonoids. Differences between the medical performance of isolated compounds like cannabidiol (CBD) or THC and full-spectrum plant extracts are notable. Indeed, the superiority of the last one is provoked by the synergy between various different compounds. This improved medicinal effect is called the entourage effect.

From: “Entourage Effect and Analytical Chemistry: Chromatography as a Tool in the Analysis of the Secondary Metabolism of Cannabis sativa L” (2023, paywalled)

https://pubmed.ncbi.nlm.nih.gov/36330630/

This 2023 review discusses the entourage effect. Is it just a marketing term used by the industry, or is there more to it?

Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn’t (2023)
Abstract
The ‘entourage effect’ term was originally coined in a pre-clinical study observing endogenous bio-inactive metabolites potentiating the activity of a bioactive endocannabinoid. As a hypothetical afterthought, this was proposed to hold general relevance to the usage of products based on Cannabis sativa L.
The term was later juxtaposed to polypharmacy pertaining to full-spectrum medicinal Cannabis products exerting an overall higher effect than the single compounds. Since the emergence of the term, a discussion of its pharmacological foundation and relevance has been ongoing.
Advocates suggest that the ‘entourage effect’ is the reason many patients experience an overall better effect from full-spectrum products. Critics state that the term is unfounded and used primarily for marketing purposes in the Cannabis industry.
… We propose that the ‘entourage effect’ is explained by traditional pharmacological terms pertaining to other plant-based medicinal products and polypharmacy in general (e.g., synergistic interactions and bioenhancement).

To the best of our knowledge, the ‘entourage effect’ term was used for the first time in a pre-clinical study performed by Ben-Shabat et al. in 1998 [2]. They found that endogenous metabolites (i.e., fatty acid glycerol esters), which are otherwise individually pharmacologically inactive, potentiated the activity of the endocannabinoid 2-AG when tested collectively in different in vitro and in vivo studies.
The potentiated effect was only observed at specific metabolite concentration ranges. This was as a hypothetical afterthought described as the ‘entourage effect’ and proposed to potentially be of broad relevance to the medicinal use of Cannabis-based products.
The authors referred to bioactive compounds derived from plants as being accompanied by chemically related compounds (i.e., ‘entourage compounds’), the latter being bio-inactive when administered individually.
The observations by Ben-Shabat et al. could therefore potentially lead to findings suggesting that plant products exert effects that resemble those found in nature more than isolated single compounds from the plant [2,3].
… The application of the ‘entourage effect’ term in the literature was later on juxtaposed with polypharmacy more broadly, pertaining to full-spectrum medicinal Cannabis products, exerting an overall higher effect compared to single compounds (e.g., THC and CBD) isolated from the plant or their synthetic analogues.

2.1. Pharmacokinetic and Pharmacodynamic Interactions
In recent decades, research has focused highly on discovering and determining the pharmacological effects involved in the ‘entourage effect’ [8]. The exact mechanisms of actions are still unknown; however, in general, they are believed to involve pharmacokinetic and pharmacodynamic interactions between the compounds of the winterized extract, that is, with plant waxes removed but cannabinoids and auxiliary compounds like terpenes and flavonoids preserved.
Interactions occur when one compound’s activity is affected by other compounds either negatively or positively. Drug interactions can be of a pharmacokinetic and pharmacodynamic nature, which collectively can exert both beneficial and adverse clinical outcomes.
Pharmacokinetic interactions affect the involved compounds’ absorption, distribution, metabolism, and excretion (ADME), ultimately impacting their bioavailability. Pharmacodynamic interactions between compounds of the full-spectrum extract affect the efficacy of the dosed medicine. These interactions happen due to differences in receptor/enzyme targets and/or binding affinities that either enhance or suppress the bioactivity of other involved compounds [9,10,11].
2.2. Additive, Synergistic, and Antagonistic Effects
Multiple types of combinatory effects are possible between the Cannabis compounds, including additive effects and synergistic as well as antagonistic interactions [9]. Additive effects between compounds are a pure summation of the individual compounds’ effects.
Antagonistic interactions result in a combinatory effect lower than the sum of individual effects. This is often considered negative in the context of therapeutic effect but can be beneficial if the dampened antagonized effect reduces unwanted adverse effects.
Synergistic interactions are the result of two or more compounds working in concert to cause a potentiated effect greater than the sum of their individual effects [12]. The ‘entourage effect’ is often described as being caused by beneficial synergistic effects, while antagonistic effects or additive adverse effects often are avoided in the discussion [7].
Underlying mechanisms of actions resulting in such synergistic effects, in addition to the elimination of adverse effects, can, as mentioned above, be of pharmacokinetic and pharmacodynamic origin [12,13,14].
2.3. Bioenhancers
Bioavailability refers to the fraction of a drug that reaches the systemic circulation and ultimately its therapeutic target(s). Bioenhancers increase bioavailability, thus enabling the drug to reach its therapeutic response at a lower dose, carrying the additional benefit of reducing the likelihood of adverse effects [15]. For a bioactive compound to exert its full therapeutic potential, its absorption and resultant bioavailability is paramount.
Depending on the route of administration, the oral route being the most restrictive, limitations in permeability, water solubility, and first-pass metabolism in the liver can decrease the compound’s bioavailability. Cannabinoids are intrinsically prone to poor bioavailability as a result of their lipophilic chemical nature and thus poor water solubility as well as the reported first-pass metabolism of both CBD and THC [16].
Bioenhancer mechanisms of actions can therefore involve, e.g., the enhancement of absorption, inhibition of drug efflux membrane transporters, and inhibition of cytochrome P-450 (CYP450) liver enzymes.
Examples of bioenhancers of natural origin are, e.g., grapefruit juice, citric acid, aloe vera, flavonoid curcumin, menthol, and eicosapentaenoic fatty acid. These are, among many others, applied as excipients in different final drug products in traditional pharmacology [17,18].

Two types of ‘entourage effects’ have been defined in relation to Cannabis-derived compounds: ‘intra-entourage’ and ‘inter-entourage’. The former refers to either cannabinoid-to-cannabinoid or terpene-to-terpene interactions, and the latter refers to cannabinoid-to-terpene interactions [23].

CB1: cannabinoid receptor 1; CB2: cannabinoid receptor 2.

THC itself has been reported to be a partial agonist of both CB1 and CB2, in addition to possessing affinity and exerting effects at other targets, observed across numerous pre-clinical studies (Table A1).
THC can exert mixed agonistic and antagonistic effects depending on different factors such as cell type, receptor expression state, and the presence of other ligands with affinity for the same targets as THC (e.g., endocannabinoids or other cannabinoids derived from the Cannabis plant).
The concentration of THC in relation to other potentially co-administered compounds (i.e., ‘entourage compounds’) also impacts the pharmacological effect [24].
CBD binds to a multitude of targets (summarized in Table A1) and as such possesses a promiscuous and complex pharmacological profile [25]. The polypharmacology of CBD is under extensive investigation for a variety of postulated pharmacological effects across multiple pathologies (e.g., neurological, neuropsychiatric, and inflammatory disorders), explaining why more data are available on this compound [26,27].
Some of CBD’s mechanisms of action, such as binding to CB1 as an allosteric negative modulator [28], can impact the bioactivity of THC. This has led to the proposal that CBD is an ‘entourage compound’ [4,5,29]. CBD additionally can impact the pharmacokinetics of THC by, e.g., inhibiting some hepatic CYP enzymes.
As such, the metabolism of THC into its more potent psychoactive metabolite (i.e., 11-OH-THC) will be delayed [30,31]. CBD furthermore can modulate endocannabinoid pharmacokinetics by inhibiting fatty acid amide hydrolase (FAAH), thus inhibiting the degradation of AEA [32].
Terpenes have also been referred to as ‘entourage compounds’ due to their ability to, e.g., increase blood–brain barrier permeability, thus increasing the pharmacokinetic properties of, e.g., THC [30,33].
… Flavonoids are another group of compounds present in Cannabis, and more than 20 different flavonoids have been identified [34]. The bioactivities and therapeutic potentials of these compounds have not yet been studied in depth. However, Cannaflavins A-C have been reported to possess anti-inflammatory, neuroprotective, anti-cancer, and anti-viral effects.
These compounds are therefore likely to contribute to the collective therapeutic effect exerted by the administration of a Cannabis-derived extract and as such could be perceived as ‘entourage compounds’ too.
The abovementioned observations, among others, have led to the proposal that THC can be perceived as a ‘silver bullet’, while the additional compounds derived from Cannabis can be perceived as a collective ‘synergistic shotgun’ [4,5,30].

THC and CBD Combinatory Effects
Research showing beneficial therapeutical effects from co-administering THC and CBD, mainly in the form of the Cannabis-based medicinal product Sativex^® (i.e., nabiximol), has by some been interpreted as supporting evidence of the ‘entourage effect’.
Sativex^® contains an almost equal ratio of THC and CBD, in addition to other minor compounds present in trace amounts. One heavily referenced example is the randomized controlled trial (RCT) by Johnson et al. [52] assessing the analgesic effect of Sativex^® compared to a THC-predominant extract and placebo in cancer patients.
Sativex^® exerted significant analgesic effects compared to both the THC extract and placebo. As the only salient difference was the presence of CBD in Sativex^®, it was proposed that the enhanced analgesic effect was a result of synergistic effects between THC and CBD.

Further research failed to reproduce the findings, possibly because additional bioactive compounds were present in the extract:

Sepulveda et al. [53] reported differential effects of CBD and THC regarding chemotherapy-induced neuropathic pain reduction. In general, the administration of pure THC or a high-THC extract was most effective. Pure CBD had little effect, whereas a high-CBD extract was more effective; however, it was not as potent as the high-THC extract. These differential effects might be a result of additional bioactive compounds present in the extract.
…Two significant effective synergistic interacting extract fractions contained the following: (1) mainly CBD (98.3%) and low concentrations of THC (0.3%), CBG (0.2%), and a trace amount of cannabidivarin (CBDV) (0.09%) and (2) mainly CBG (58.8%) and CBD (38.2%) as well as low concentrations of THC (0.7%) and CBC (0.4%), respectively.
The synergistic effects were dependent on the relative ratios between the cannabinoids. These findings were proposed by the authors to not only be caused by additive effects of CBD in both fractions but also potential synergistic interactions between CBD and CBG, which has been reported by other research groups [63].
The synergy might also be a result of the activation of multiple targets and pathways besides CB1 and CB2 receptors. The depletion of non-active and antagonistic compounds from the full-spectrum extract might cause higher specific cytotoxic efficacy while reducing the concentration, and dose, of the fractions needed to exert a significant effect (i.e., a ‘contra-entourage effect’).
Raup-Konsavage et al. [64] reported that CBD did not display an ‘entourage effect’ in regard to anti-cancer effects. It was observed that pure CBD exerted an equally or more potent anti-cancer effect compared to several CBD oil extracts that additionally contained minor amounts of other cannabinoids (e.g., CBC, CBG, CBN, and THC). The authors did, however, state that these in vitro observations did not rule out potential synergistic effects arising between extract compounds.

Although it may be difficult to demonstrate in the lab, the principles are already well established in pharmacology, where it is known as “polypharmacy”:

Although evidence exists that indicates the enhanced therapeutic efficacy of extracts compared to single compounds, the question remains whether this proves the existence of the ‘entourage effect’ or if it is merely a sign of specific compound combinations exerting enhanced therapeutic efficacy (as, e.g., shown in the study by Mazuz et al. [62]).
Traditional pharmacology describes this as polypharmacy, and it is the basis for active pharmaceutical ingredient (API) combinations exerting combinatory beneficial pharmacological effects.
In this context, existing pharmacological terms, like additive effects, synergistic interactions, and bioenhancers, seem to be perfectly applicable in explaining the pharmacological effects underlying the proclaimed entourage effect term. For that reason, it appears unnecessary to introduce a term such as ‘entourage effect’ exclusively to Cannabis-based products.

Pharmacology would refer to full-spectrum hemp extracts as a “dirty drug”, which is hilarious.

They really wouldn’t see eye to eye with the physicians of old.

… In pharmacology, the informal term “dirty drug” refers to a drug that targets multiple targets within the body and exerts a wide range of effects, both desired and undesired.
… “Dirty drugs” additionally raise the risk of drug–drug interactions when co-administered with other drugs. This is particularly critical, when administering drugs with a narrow therapeutic index. Several cannabinoids are known to be metabolized by hepatic CYP enzymes, which can either inhibit or enhance other compounds’, or drugs’, metabolism and vice versa.
One of the most commonly administered cannabinoids, CBD, is an inhibitor of a CYP subtype responsible for the metabolism of several antidepressants and opioids. Consequently, the hypothetical scenario of CBD co-administration with other active compounds (e.g., antidepressants or opioids) may result in an increase in API serum concentrations, ultimately affecting the resultant pharmacological response [7].
For that reason, pharmaceutical companies aim to avoid having these so-called “dirty” drugs in their pipeline and instead focus on designing drugs as selectively as possible. On the contrary, opioids and cannabinoids have been observed to exert synergistic effects in the case of, e.g., pain management, when co-administered.
Thus, knowledge of specific active compound combinations exerting beneficial combinatory effects might provide alternative treatment options for patients with unmet medical needs. This might even lead to lower drug doses needed to provide a therapeutic effect, as, e.g., observed by the opioid-sparing effect of cannabinoids [68].
Many diseases are caused by a multifactorial causality, where single-compound medicinal products often fail to target all the disease-affected targets and as a result fail to manage the disease effectively.
It has therefore been proposed that multi-compound products, such as Cannabis extracts, can provide beneficial effects in the management of such multifactorial diseases, being perceived as a more holistic treatment approach (e.g., [12,69]).
… Lehar et al. [70] observed that combinations of selected compounds resulted in synergistic effects and improved therapeutic selectivity as a result of multi-target effects. Consequently, the therapeutic dose could be reduced, additionally minimizing occurrences of adverse effects often associated with the administration of high drug doses.
In fact, treatment with Cannabis extracts has been proposed to reduce polypharmacy, which is the realistic scenario for many patients living with multiple diseases and related symptoms.
More: https://pmc.ncbi.nlm.nih.gov/articles/PMC10452568/

3.0 Parting shots

3.1 A step closer to the digital panopticon

Universal, state-mandated warrantless searches of your handsets. A hard pass from me. They already spy on us enough, whilst the real child-abusers are largely let off the hook.

Why the police ignored the rape gangs - UnHerd

Hell no!

The only certainty is that this move into monitoring, control, and censorship is not motivated in the least by child safety considerations.

UK Plans To JAIL Tech CEOs Who Refuse To SPY On Every Phone
Steve Watson
9th June 2026
New measures would compel client-side inspection of every photo, video and message on devices, escalating the digital ID lockdown already plotted for British smartphones in coordination with major technology firms.
Privacy advocates warn the “child safety” framing masks a broader drive to turn personal phones into mandatory surveillance endpoints, with criminal penalties aimed at any executive who resists.
Reclaim The Net, an organization dedicated to countering online censorship and digital surveillance, flagged the draft legislation in recent updates.
The group described how UK authorities are preparing to imprison tech executives for up to five years under the Online Safety Act if companies refuse to build and deploy scanners capable of reviewing every piece of content on user devices.
The push targets expanded “client-side scanning” features, requiring devices to inspect material before it is sent or received.
Existing tools from Apple and Google, such as nudity detection in Messages or sensitive content warnings, would be broadened into comprehensive, always-active systems. Non-compliance would trigger direct penalties against company leadership rather than the firms alone.
Former Home Office safeguarding minister Jess Phillips, who resigned in May, had publicly pressed for faster action. She stated it had taken a year to secure agreement even to threaten legislation in this space and expressed frustration that promised timelines kept slipping, questioning how many children had gone without protections while focus remained on tech company objections.
… Without compliance, devices would default to restricted child-locked modes, limiting core features like unrestricted messaging, streaming and browsing. The approach effectively creates a chokehold on software and internet access for anyone unwilling to submit to centralized identity verification.
More: https://modernity.news/2026/06/09/uk-plans-to-jail-tech-ceos-who-refuse-to-spy-on-every-phone/

3.2 In need of urgent medical care? First, you need to convince the digital receptionist that you are ill enough

Digital triage = rationing

Pepper was adapted to support reception teams. — **“Press #9 if you have an axe in your head”.**

Anyone who's been caught in an automated phone loop of despair because their problem doesn't match any of the available options will understand how frustrating it can be.

Older Person Computer Struggle Stock ... — Answer incorrectly, and you effectively get thrown out.

NHS replaces A&E receptionists with iPads
Patients’ groups have warned that iPad-style check-ins could lead to a ‘computer says no’ culture - John Lamb/Photodisc
Accident & Emergency (A&E) patients will be forced to complete online questionnaires before getting treatment under NHS plans for iPad-style check-ins.
The “high-tech concierge service” will act as a virtual receptionist, requiring patients to answer questions at kiosks or tablets to help determine what help they need.
Sir Jim Mackey, the head of NHS England, said the rollout was part of efforts to bring “order” to emergency care, prioritising the most urgent cases and sending others elsewhere.
Under the system, which hospitals are being urged to introduce by winter, patients arriving at A&E will answer questions about symptoms and medical history on self-check-in screens or tablets.
While some patients will be prioritised for immediate treatment, others will be redirected to pharmacies or GPs, or given appointments to return later.

Well, that’s alright then:

Emergency cases arriving by ambulance or requiring immediate life-saving care would bypass the system and receive urgent clinical treatment, health officials said.
Sir Jim urged health service leaders to rapidly adopt the “digital triage” system developed by NHS England.
In a speech to the NHS ConfedExpo conference in Manchester, Sir Jim said it was his “personal obsession” to bring “order” into urgent and emergency care, reducing long waits and overcrowding.
However, patients’ groups raised fears of a “computer says no” approach to emergency medicine, warning vulnerable patients could struggle with digital screening and be incorrectly diverted away from A&E.

It’s easier to introduce gimmicks and rationing than to ask why you are being overwhelmed with patients in the first place, despite mass vaccination programs, community diagnosis units, and prescription drugs for all.

#Baffled

“The big prize for this coming winter is shifting to introducing many more appointments into urgent care,” Sir Jim said, adding that the combination of this with digital triage could have an “enormous” impact on patients in the coming months.
Sir Jim Mackey wants all NHS A&E services in England to have ‘digital triage’ - Geoff Pugh
Dennis Reed, director of Silver Voices, which campaigns for people aged over 60, said: “I’m really worried about the patients who will struggle with this, or who may not be able to describe their symptoms properly, when what they need is a clinician who can see them and ask the right questions.
More: https://www.msn.com/en-gb/health/other/nhs-replaces-a-e-receptionists-with-ipads/ar-AA25k9CK

4.0 Disclaimer

This site is strictly an informational website that reviews research on potential therapeutic agents. It does not advertise, provide medical advice, diagnosis, or treatment, nor does it promote any of these as potential treatments or make claims about efficacy. Its content is aimed at researchers, registered medical practitioners, nurses, or pharmacists. This content is not a substitute for professional medical advice, diagnosis, or treatment.

Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this website.

Always consult a qualified health provider before introducing or stopping any medications, as any possible drug interactions or effects will need to be considered.

Any extracts quoted in the previous article are for non-commercial research and educational purposes only and may be subject to copyright by their respective owners.

5.0 References

Drug licensing factsheet: cannabis, CBD and other cannabinoids. GOV.UK. Accessed June 13, 2026. https://www.gov.uk/government/publications/cannabis-cbd-and-other-cannabinoids-drug-licensing-factsheet/drug-licensing-factsheet-cannabis-cbd-and-other-cannabinoids

“Cannabidiol Market Size And Share | Industry Report, 2033.” May 2026. https://www.grandviewresearch.com/industry-analysis/cannabidiol-cbd-market.

“A History Of Hemp - HEMPEN ORGANIC Organic.” April 3, 2023. https://www.hempen.co.uk/a-history-of-hemp/.

Sideris, Alexandra, and Lisa V. Doan. “An Overview of Cannabidiol.” Anesthesia & Analgesia 138, no. 1 (2024): 54. https://doi.org/10.1213/ANE.0000000000006584.

British Hemp Alliance. “Hemp History | Discover Hemp’s Legacy Today.” Accessed June 13, 2026. https://www.britishhempalliance.co.uk/hemp-history.

Hempies. “Why Was Hemp Made Illegal? | Politics & Misinformation.” October 18, 2024. https://hempies.com.au/blogs/news/why-was-hemp-made-illegal.

Why Was Hemp Banned in the United States in 1937? - HempAware. Hemp History. June 4, 2024. 225. https://hempaware.com/why-was-hemp-banned-in-the-united-states-in-1937/.

Releaf. “The Fascinating History of Hemp Prohibition.” August 4, 2023. https://releaf.co.uk/education/cannabis-101/history/the-fascinating-history-of-hemp-prohibition.

Corroon J, Bradley R, Grant I, et al. Lifetime Cannabis Use and Incident Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. Hypertension. 2025;82(10):1641-1652. doi:10.1161/HYPERTENSIONAHA.125.25005

Jadoon KA, Tan GD, O’Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2(12):e93760. doi:10.1172/jci.insight.93760

Commentaires

Anonyme15 juin 2026 à 15:38

David Cowley
University of Lincoln
de : https://www.researchgate.net/profile/David-Cowley-10
My studies at the University of Hertfordshire included plant pathology, biochemistry, and genetics. I then transitioned to studying animal biochemistry and pathophysiology. Plant-based therapeutics link the two specialisms. Apart from co-writing, I write a BioMed literature review newsletter and discuss various topics: oncology, neurology, CVD, immunology, BioChem, and therapeutics: https://doorlesscarp953.substack.com/
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