The American Society of Clinical Oncology (ASCO) and the Society for Integrative Oncology have collaborated to develop guidelines for the application of integrative approaches in the management of:
- anxiety,
- depression,
- fatigue,
- use of cannabinoids and cannabis in patients with cancer.
These guidelines provide evidence-based recommendations to improve outcomes and quality of life by enhancing conventional cancer treatment with integrative modalities.
All studies that informed the guideline recommendations were reviewed by an Expert Panel which was made up of a patient advocate, an ASCO methodologist, oncology providers, and integrative medicine experts. Panel members reviewed each trial for quality of evidence, determined a grade quality assessment label, and concluded strength of recommendations.
The findings show:
- Strong recommendations for management of cancer fatigue during treatment were given to both in-person or web-based mindfulness-based stress reduction, mindfulness-based cognitive therapy, and tai chi or qigong.
- Strong recommendations for management of cancer fatigue after cancer treatment were given to mindfulness-based programs.
- Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial.
- The recommended modalities for managing anxiety included Mindfulness-Based Interventions (MBIs), yoga, hypnosis, relaxation therapies, music therapy, reflexology, acupuncture, tai chi, and lavender essential oils.
- The strongest recommendation in the guideline is that MBIs should be offered to people with cancer, both during active treatment and post-treatment, to address depression.
The authors concluded that the evidence for integrative interventions in cancer care is growing, with research now supporting benefits of integrative interventions across the cancer care continuum.
I am sorry, but I find these guidelines of poor quality and totally inadequate for the purpose of providing responsible guidance to cancer patients and carers. Here are some of my reasons:
- I know that this is a petty point, particularly for me as a non-native English speaker, but what on earth is an INTEGRATIVE THERAPY? I know integrative care or integrative medicine, but what could possibly be integrative with a therapy?
- I can vouch for the fact that the assertion “all studies that informed the guideline recommendations were reviewed” is NOT true. The authors seem to have selected the studies they wanted. Crucially, they do not reveal their selection criteria. I have the impression that they selected positive studies and omitted those that were negative.
- The panel of experts conducting the research should be mentioned; one can put together a panel to show just about anything simply by choosing the right individuals.
- The authors claim that they assessed the quality of the evidence, yet they fail to tell us what it was. I know that many of the trials are of low quality and their results therefore less than reliable. And guidance based on poor-quality studies is misguidance.
- The guidelines say nothing about the risks of the various treatments. In my view, this would be essential for any decent guideline. I know that some of the mentioned therapies are not free of adverse effects.
- They also say nothing about the absolute and relative effect sizes of the treatments they recommend. Such information would ne necessary for making informed decisions about the optimal therapeutic choices.
- The entire guideline is bar any critical thinking.
Overall, these guidelines provide more an exercise in promotion of dubious therapies than a reliable guide for cancer patients and their carers. The ASCO and the Society for Integrative Oncology should be ashamed to have given their names to such a poor-quality document.
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Can the MPC process in breast cancer be controlled by cannabis?
There is currently no direct scientific evidence showing that cannabis can explicitly control or target the Mitochondrial Pyruvate Carrier (MPC) process in breast cancer cells.
While both the MPC and cannabis are major areas of interest in oncology research, they sit in separate branches of study. Cannabis compounds do not have a proven, direct mechanism for turning the MPC “on” or “off.”
However, cannabis profoundly disrupts general mitochondrial metabolism and energy production in breast cancer cells through adjacent pathways.
When researchers look at how cannabis compounds—primarily Cannabidiol (CBD) and Tetrahydrocannabinol (THC)—interact with breast cancer mitochondria, they observe several specific, documented metabolic effects: [1]
1. Disrupting the Citric Acid (Krebs) Cycle
The Action:
Metabolomics studies examining Cannabis sativa extracts on human breast cancer cells (specifically the MCF-7 cell line) show that cannabinoids cause a widespread inhibition of substrates within the Citric Acid Cycle. [2, 3]
The Mitochondrial Impact:
Even though it is unknown if this inhibition starts precisely at the MPC gateway, cannabis effectively “sabotages” the downstream machinery that processes pyruvate, starving the cancer cell of its required energy. [4]
2. Altering the Mitochondrial Redox State
The Action:
CBD alters the internal balance of NAD(P)H and the mitochondrial redox state in breast cancer cells.
The Mitochondrial Impact:
This shift destroys the mitochondrial membrane potential. When this electrical potential collapses, the mitochondria can no longer properly import or utilize metabolites (like pyruvate) and instead trigger the intrinsic pathway for programmed cell death (apoptosis). [5, 6, 7, 8]
3. Inducing Mitochondrial Calcium Overload
The Action:
Cannabinoids can force a massive influx of intracellular calcium directly into the mitochondria of breast cancer cells.
The Mitochondrial Impact:
While healthy breast cells are largely unaffected by this concentration, malignant breast cells experience mitochondrial calcium overload, which halts their metabolic activity and reduces cell viability. [2, 9]
4. Selective Cytotoxicity
The Action:
In laboratory settings, cannabis extracts exhibit selective cytotoxicity. They aggressively disrupt the mitochondrial pathways of active breast cancer cells while leaving non-cancerous mammary epithelial cells mostly unharmed. [2, 10]
The Current Reality:
In Vitro vs. In Vivo it is crucial to emphasize that almost all data linking cannabis to breast cancer mitochondrial disruption comes from preclinical in vitro (petri dish) cell cultures and animal models. [5, 11]
The Human Gap:
Clinical trials have not yet proven that smoking, vaping, or ingesting cannabis delivers a high enough, localized concentration of cannabinoids to a human breast tumor to replicate these metabolic anti-cancer effects. [11, 12]
Standard Use:
Currently, oncologists recommend cannabis primarily for palliative symptom control (such as managing chemotherapy-induced nausea, pain, and appetite loss), rather than as a primary metabolic cancer treatment. [11, 13]
If you are trying to understand this for a specific real-world application, please let me know:
Is this a general scientific interest in cancer metabolomics, or are you looking into integrative options for an active diagnosis?
Are you evaluating a specific type of cannabis product (like high-dose Rick Simpson Oil/RSO, CBD isolate, or standard medical cannabis)?
[1] [https://www.genesispub.org](https://www.genesispub.org/jctr/the-impact-of-cannabinoids-on-breast-cancer-cell-lines-a-meta-analysis-and-systematic-review-of-antitumoral-effects)
[2] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC11471428/)
[3] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC10196869/)
[4] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12984507/)
[5] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12023523/)
[6] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9600568/)
[7] [https://www.newswise.com](https://www.newswise.com/articles/mitochondrial-antioxidant-found-to-drive-breast-cancer-metastasis)
[8] [https://aacrjournals.org](https://aacrjournals.org/mct/article/10/7/1161/91099/Cannabidiol-Induces-Programmed-Cell-Death-in)
[9] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC8159073/)
[10] [https://pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/16818634/)
[11] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12984507/)
[12] [https://www.mbcalliance.org](https://www.mbcalliance.org/guestblogposts/force-content/cannabis-use-among-breast-cancer-patients/)
[13] [https://resources.healthgrades.com](https://resources.healthgrades.com/pro/cbd-and-breast-cancer-what-your-patients-should-know)
what concentrations of cannabinouds would be needed to affect a cancerous mitochondria invivo?
To induce mitochondrial dysfunction, collapse membrane potential, and trigger apoptosis in a cancerous cell in vivo (inside a living organism), tissue concentrations of cannabinoids generally must reach low-to-mid micromolar ($\mu M$) ranges, specifically between 4 $\mu M$ and 30 $\mu M$. [1, 2]
Achieving and maintaining this specific concentration inside a solid tumor within a living body represents the primary obstacle in translating laboratory cannabis research into actual human cancer therapies.
The Concentration Thresholds (The Micromolar Gap)
In animal model xenografts and preclinical studies, the exact dose required depends heavily on the specific cannabinoid and the targeted mitochondrial mechanism:
Mitochondrial Respiration Decoupling (4 to 6 $\mu M$):
This is the minimum threshold where cannabinoids actively disrupt energy. For example, research demonstrates that 4 $\mu M$ of Cannabidiol (CBD) significantly shuts down basal respiration and ATP production in gastrointestinal cancer cells, while 6 $\mu M$ collapses the mitochondrial transmembrane potential in colorectal cancer cells. [1]
Lethal Calcium Overload (>10 to 30 $\mu M$):
To trigger the specific mechanism where CBD forces the VDAC1 channel open—causing a massive, fatal influx of calcium that physically ruptures the cancer mitochondria—concentrations must exceed 10 $\mu M$, frequently requiring 15 to 30 $\mu M$ to achieve widespread tumor cell death. [2, 3, 4, 5]
THC Cytotoxicity (15 to 40 $\mu M$):
For Delta-9-THC to induce autophagic-dependent necrosis via mitochondrial stress, studies show a requirement of 15 $\mu M$ to 40 $\mu M$. [6, 7]
Why In Vivo Concentration is Hard to Achieve
While hitting a $10\ \mu M$ concentration in a plastic petri dish is simple, achieving it inside a living human tumor is highly complex due to several biological hurdles:
| Biological Barrier [8]
| The Impact on Cannabinoid Concentration
| High Plasma Protein Binding
| Cannabinoids are extremely lipophilic (fat-loving) and bind 90% to 95% to proteins (like albumin) in the blood. Only the tiny fraction of “free” unbound cannabinoid can actually penetrate a tumor to interact with cancer mitochondria.
| Rapid Hepatic Metabolism
| The liver aggressively metabolizes THC and CBD via CYP450 enzymes on their first pass, rapidly dropping active blood concentrations before they can reach peripheral tissues.
| Bioavailability Ceilings
| Standard oral ingestion of cannabis oils or edibles yields a human plasma concentration that peaks in the low nanomolar ($nM$) range (typically under $0.1\ \mu M$), which is 40 to 100 times lower than the threshold required to destroy cancer mitochondria. |
How Researchers Attempt to Force These Concentrations
To overcome these barriers and achieve true $in\ vivo$ mitochondrial destruction, preclinical animal studies do not rely on standard administration methods. Instead, they use aggressive dosing protocols:
1. High-Dose Systemic Injections: Animal models typically require direct intraperitoneal or intravenous doses ranging from 10 mg/kg to 100 mg/kg of body weight daily to force blood levels into the micromolar range. [2, 9]
2. Direct Intratumoral Delivery: Some studies bypass the bloodstream entirely, injecting concentrated cannabinoid solutions directly into the tumor mass to ensure the mitochondria are completely saturated.
If you are evaluating this data for a specific practical application, please let me know:
Are you looking into this to understand the science behind highly concentrated cannabis protocols (such as Rick Simpson Oil/RSO)?
Are you interested in how these required concentrations compare to standard commercial CBD or medical cannabis dosing?
[1] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC8159073/)
[2] [https://www.mdpi.com](https://www.mdpi.com/2223-7747/14/4/585)
[3] [https://www.frontiersin.org](https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.725136/full)
[4] [https://pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/12533310/)
[5] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12651666/)
[6] [https://www.sciencedirect.com](https://www.sciencedirect.com/science/article/pii/S1043661822005497)
[7] [https://www.mdpi.com](https://www.mdpi.com/2072-6694/12/7/1985)
[8] [https://pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/36944160/)
[9] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC7037210/)
Can cannabinoids be delivered in and LNP envelope ?
Yes, cannabinoids can be successfully delivered inside Lipid Nanoparticle (LNP) envelopes. Overcoming the “micromolar gap” inside a living organism is precisely why biotech firms and oncology researchers use nanotechnology. [1, 2, 3]
Because cannabinoids like CBD and THC are highly lipophilic (fat-loving), they are naturally perfectly suited to blend into the fatty, oily core of a lipid nanoparticle. [2, 4]
Using LNPs or specialized Solid Lipid Nanoparticles (SLNs) alters how cannabinoids act inside a living body, directly solving the challenges of targeting cancerous mitochondria: [3, 5]
1. Bypassing “Plasma Protein Binding”
The Problem:
Free cannabinoids bind up to 95% to blood proteins, leaving almost nothing to penetrate the tumor.
The LNP Solution:
The lipid envelope physically shields the cannabinoid from blood proteins. The compound remains safely hidden inside the nano-capsule until it reaches the target site. [6]
2. Exploiting the EPR Effect for Tumor Accumulation
The Mechanism:
Tumor blood vessels are notoriously “leaky” and poorly formed. LNPs are engineered at a microscopic scale (usually around 100 to 150 nanometers). [7, 8]
The Advantage:
This precise size allows them to slip through the gaps in tumor blood vessels and get trapped directly inside the tumor tissue. This passive targeting significantly builds up local cannabinoid concentrations, hitting the 4 μ M to 30 μ M mark required to destroy mitochondria without oversaturating healthy organs. [6, 9, 10]
3. Evading Liver Elimination
The Advantage:
Ingested or injected free cannabinoids are rapidly destroyed by liver enzymes on their first pass. LNPs protect the active ingredients, drastically extending their half-life in the bloodstream and allowing more of the dose to reach the tumor. [3, 5]
4. Enhancing Cellular Ingestion (Endocytosis)
The Advantage:
Cancer cell membranes are made of lipids. When an LNP encounters a cancer cell, its lipid envelope fuses directly with the cell membrane or triggers endocytosis (where the cell swallows the nanoparticle whole). Once inside, the nano-envelope breaks down, dumping a massive, localized payload of cannabinoids directly into the cytoplasm to overwhelm the mitochondria. [6, 7]
Current State of the Science
In advanced oncology research, scientists are taking this a step further by using LNPs for dual-delivery protocols. For example, studies highlight the formulation of NLC-CBD-PTX—nanoparticles that co-encapsulate both Cannabidiol and Paclitaxel (a standard chemotherapy drug). [11, 12, 13]
The nanoparticle safely delivers both compounds simultaneously into tumor lines like melanoma, allowing CBD to stress the mitochondria and sensitize the cell, which dramatically increases the chemotherapy’s ability to kill the tumor. [1, 12, 13]
If you are exploring this topic to understand how close these technologies are to standard use, let me know:
* Are you looking into this from a pharmaceutical development perspective, or trying to see if these options are available to patients?
* Would you like to know more about the regulatory hurdles or current human clinical trial statuses for lipid-encapsulated cannabinoid therapies?
[1] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12776580/)
[2] [https://www.pharmaexcipients.com](https://www.pharmaexcipients.com/news/encapsulating-cannabinoids-lnp-part-2/)
[3] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC10141492/)
[4] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12524416/)
[5] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC11083812/)
[6] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC11566655/)
[7] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC9713120/)
[8] [https://ouci.dntb.gov.ua](https://ouci.dntb.gov.ua/en/works/98aYAGw7/)
[9] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12776580/)
[10] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12532965/)
[11] [https://www.biorxiv.org](https://www.biorxiv.org/content/10.1101/2024.10.15.618512v1.full-text)
[12] [https://www.biorxiv.org](https://www.biorxiv.org/content/10.1101/2024.10.15.618512v1.full-text)
[13] [https://pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12138705/)